TY - JOUR
A1 - Mantzouki, Evanthia
A1 - Lurling, Miquel
A1 - Fastner, Jutta
A1 - Domis, Lisette Nicole de Senerpont
A1 - Wilk-Wozniak, Elzbieta
A1 - Koreiviene, Judita
A1 - Seelen, Laura
A1 - Teurlincx, Sven
A1 - Verstijnen, Yvon
A1 - Krzton, Wojciech
A1 - Walusiak, Edward
A1 - Karosiene, Jurate
A1 - Kasperoviciene, Jurate
A1 - Savadova, Ksenija
A1 - Vitonyte, Irma
A1 - Cillero-Castro, Carmen
A1 - Budzynska, Agnieszka
A1 - Goldyn, Ryszard
A1 - Kozak, Anna
A1 - Rosinska, Joanna
A1 - Szelag-Wasielewska, Elzbieta
A1 - Domek, Piotr
A1 - Jakubowska-Krepska, Natalia
A1 - Kwasizur, Kinga
A1 - Messyasz, Beata
A1 - Pelechata, Aleksandra
A1 - Pelechaty, Mariusz
A1 - Kokocinski, Mikolaj
A1 - Garcia-Murcia, Ana
A1 - Real, Monserrat
A1 - Romans, Elvira
A1 - Noguero-Ribes, Jordi
A1 - Parreno Duque, David
A1 - Fernandez-Moran, Elisabeth
A1 - Karakaya, Nusret
A1 - Haggqvist, Kerstin
A1 - Demir, Nilsun
A1 - Beklioglu, Meryem
A1 - Filiz, Nur
A1 - Levi, Eti E.
A1 - Iskin, Ugur
A1 - Bezirci, Gizem
A1 - Tavsanoglu, Ulku Nihan
A1 - Ozhan, Koray
A1 - Gkelis, Spyros
A1 - Panou, Manthos
A1 - Fakioglu, Ozden
A1 - Avagianos, Christos
A1 - Kaloudis, Triantafyllos
A1 - Celik, Kemal
A1 - Yilmaz, Mete
A1 - Marce, Rafael
A1 - Catalan, Nuria
A1 - Bravo, Andrea G.
A1 - Buck, Moritz
A1 - Colom-Montero, William
A1 - Mustonen, Kristiina
A1 - Pierson, Don
A1 - Yang, Yang
A1 - Raposeiro, Pedro M.
A1 - Goncalves, Vitor
A1 - Antoniou, Maria G.
A1 - Tsiarta, Nikoletta
A1 - McCarthy, Valerie
A1 - Perello, Victor C.
A1 - Feldmann, Tonu
A1 - Laas, Alo
A1 - Panksep, Kristel
A1 - Tuvikene, Lea
A1 - Gagala, Ilona
A1 - Mankiewicz-Boczek, Joana
A1 - Yagci, Meral Apaydin
A1 - Cinar, Sakir
A1 - Capkin, Kadir
A1 - Yagci, Abdulkadir
A1 - Cesur, Mehmet
A1 - Bilgin, Fuat
A1 - Bulut, Cafer
A1 - Uysal, Rahmi
A1 - Obertegger, Ulrike
A1 - Boscaini, Adriano
A1 - Flaim, Giovanna
A1 - Salmaso, Nico
A1 - Cerasino, Leonardo
A1 - Richardson, Jessica
A1 - Visser, Petra M.
A1 - Verspagen, Jolanda M. H.
A1 - Karan, Tunay
A1 - Soylu, Elif Neyran
A1 - Maraslioglu, Faruk
A1 - Napiorkowska-Krzebietke, Agnieszka
A1 - Ochocka, Agnieszka
A1 - Pasztaleniec, Agnieszka
A1 - Antao-Geraldes, Ana M.
A1 - Vasconcelos, Vitor
A1 - Morais, Joao
A1 - Vale, Micaela
A1 - Koker, Latife
A1 - Akcaalan, Reyhan
A1 - Albay, Meric
A1 - Maronic, Dubravka Spoljaric
A1 - Stevic, Filip
A1 - Pfeiffer, Tanja Zuna
A1 - Fonvielle, Jeremy Andre
A1 - Straile, Dietmar
A1 - Rothhaupt, Karl-Otto
A1 - Hansson, Lars-Anders
A1 - Urrutia-Cordero, Pablo
A1 - Blaha, Ludek
A1 - Geris, Rodan
A1 - Frankova, Marketa
A1 - Kocer, Mehmet Ali Turan
A1 - Alp, Mehmet Tahir
A1 - Remec-Rekar, Spela
A1 - Elersek, Tina
A1 - Triantis, Theodoros
A1 - Zervou, Sevasti-Kiriaki
A1 - Hiskia, Anastasia
A1 - Haande, Sigrid
A1 - Skjelbred, Birger
A1 - Madrecka, Beata
A1 - Nemova, Hana
A1 - Drastichova, Iveta
A1 - Chomova, Lucia
A1 - Edwards, Christine
A1 - Sevindik, Tugba Ongun
A1 - Tunca, Hatice
A1 - OEnem, Burcin
A1 - Aleksovski, Boris
A1 - Krstic, Svetislav
A1 - Vucelic, Itana Bokan
A1 - Nawrocka, Lidia
A1 - Salmi, Pauliina
A1 - Machado-Vieira, Danielle
A1 - de Oliveira, Alinne Gurjao
A1 - Delgado-Martin, Jordi
A1 - Garcia, David
A1 - Cereijo, Jose Luis
A1 - Goma, Joan
A1 - Trapote, Mari Carmen
A1 - Vegas-Vilarrubia, Teresa
A1 - Obrador, Biel
A1 - Grabowska, Magdalena
A1 - Karpowicz, Maciej
A1 - Chmura, Damian
A1 - Ubeda, Barbara
A1 - Angel Galvez, Jose
A1 - Ozen, Arda
A1 - Christoffersen, Kirsten Seestern
A1 - Warming, Trine Perlt
A1 - Kobos, Justyna
A1 - Mazur-Marzec, Hanna
A1 - Perez-Martinez, Carmen
A1 - Ramos-Rodriguez, Eloisa
A1 - Arvola, Lauri
A1 - Alcaraz-Parraga, Pablo
A1 - Toporowska, Magdalena
A1 - Pawlik-Skowronska, Barbara
A1 - Niedzwiecki, Michal
A1 - Peczula, Wojciech
A1 - Leira, Manel
A1 - Hernandez, Armand
A1 - Moreno-Ostos, Enrique
A1 - Maria Blanco, Jose
A1 - Rodriguez, Valeriano
A1 - Juan Montes-Perez, Jorge
A1 - Palomino, Roberto L.
A1 - Rodriguez-Perez, Estela
A1 - Carballeira, Rafael
A1 - Camacho, Antonio
A1 - Picazo, Antonio
A1 - Rochera, Carlos
A1 - Santamans, Anna C.
A1 - Ferriol, Carmen
A1 - Romo, Susana
A1 - Miguel Soria, Juan
A1 - Dunalska, Julita
A1 - Sienska, Justyna
A1 - Szymanski, Daniel
A1 - Kruk, Marek
A1 - Kostrzewska-Szlakowska, Iwona
A1 - Jasser, Iwona
A1 - Zutinic, Petar
A1 - Udovic, Marija Gligora
A1 - Plenkovic-Moraj, Andelka
A1 - Frak, Magdalena
A1 - Bankowska-Sobczak, Agnieszka
A1 - Wasilewicz, Michal
A1 - Ozkan, Korhan
A1 - Maliaka, Valentini
A1 - Kangro, Kersti
A1 - Grossart, Hans-Peter
A1 - Paerl, Hans W.
A1 - Carey, Cayelan C.
A1 - Ibelings, Bas W.
T1 - Temperature effects explain continental scale distribution of cyanobacterial toxins
JF - Toxins
N2 - Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a) and cytotoxins (e.g., cylindrospermopsin) due to their potency. Most studies examine the relationship between individual toxin variants and environmental factors, such as nutrients, temperature and light. In summer 2015, we collected samples across Europe to investigate the effect of nutrient and temperature gradients on the variability of toxin production at a continental scale. Direct and indirect effects of temperature were the main drivers of the spatial distribution in the toxins produced by the cyanobacterial community, the toxin concentrations and toxin quota. Generalized linear models showed that a Toxin Diversity Index (TDI) increased with latitude, while it decreased with water stability. Increases in TDI were explained through a significant increase in toxin variants such as MC-YR, anatoxin and cylindrospermopsin, accompanied by a decreasing presence of MC-LR. While global warming continues, the direct and indirect effects of increased lake temperatures will drive changes in the distribution of cyanobacterial toxins in Europe, potentially promoting selection of a few highly toxic species or strains.
KW - microcystin
KW - anatoxin
KW - cylindrospermopsin
KW - temperature
KW - direct effects
KW - indirect effects
KW - spatial distribution
KW - European Multi Lake Survey
Y1 - 2018
U6 - https://doi.org/10.3390/toxins10040156
SN - 2072-6651
VL - 10
IS - 4
PB - MDPI
CY - Basel
ER -
TY - JOUR
A1 - Mantzouki, Evanthia
A1 - Campbell, James
A1 - van Loon, Emiel
A1 - Visser, Petra
A1 - Konstantinou, Iosif
A1 - Antoniou, Maria
A1 - Giuliani, Gregory
A1 - Machado-Vieira, Danielle
A1 - de Oliveira, Alinne Gurjao
A1 - Maronic, Dubravka Spoljaric
A1 - Stevic, Filip
A1 - Pfeiffer, Tanja Zuna
A1 - Vucelic, Itana Bokan
A1 - Zutinic, Petar
A1 - Udovic, Marija Gligora
A1 - Plenkovic-Moraj, Andelka
A1 - Tsiarta, Nikoletta
A1 - Blaha, Ludek
A1 - Geris, Rodan
A1 - Frankova, Marketa
A1 - Christoffersen, Kirsten Seestern
A1 - Warming, Trine Perlt
A1 - Feldmann, Tonu
A1 - Laas, Alo
A1 - Panksep, Kristel
A1 - Tuvikene, Lea
A1 - Kangro, Kersti
A1 - Haggqvist, Kerstin
A1 - Salmi, Pauliina
A1 - Arvola, Lauri
A1 - Fastner, Jutta
A1 - Straile, Dietmar
A1 - Rothhaupt, Karl-Otto
A1 - Fonvielle, Jeremy Andre
A1 - Grossart, Hans-Peter
A1 - Avagianos, Christos
A1 - Kaloudis, Triantafyllos
A1 - Triantis, Theodoros
A1 - Zervou, Sevasti-Kiriaki
A1 - Hiskia, Anastasia
A1 - Gkelis, Spyros
A1 - Panou, Manthos
A1 - McCarthy, Valerie
A1 - Perello, Victor C.
A1 - Obertegger, Ulrike
A1 - Boscaini, Adriano
A1 - Flaim, Giovanna
A1 - Salmaso, Nico
A1 - Cerasino, Leonardo
A1 - Koreiviene, Judita
A1 - Karosiene, Jurate
A1 - Kasperoviciene, Jurate
A1 - Savadova, Ksenija
A1 - Vitonyte, Irma
A1 - Haande, Sigrid
A1 - Skjelbred, Birger
A1 - Grabowska, Magdalena
A1 - Karpowicz, Maciej
A1 - Chmura, Damian
A1 - Nawrocka, Lidia
A1 - Kobos, Justyna
A1 - Mazur-Marzec, Hanna
A1 - Alcaraz-Parraga, Pablo
A1 - Wilk-Wozniak, Elzbieta
A1 - Krzton, Wojciech
A1 - Walusiak, Edward
A1 - Gagala, Ilona
A1 - Mankiewicz-Boczek, Joana
A1 - Toporowska, Magdalena
A1 - Pawlik-Skowronska, Barbara
A1 - Niedzwiecki, Michal
A1 - Peczula, Wojciech
A1 - Napiorkowska-Krzebietke, Agnieszka
A1 - Dunalska, Julita
A1 - Sienska, Justyna
A1 - Szymanski, Daniel
A1 - Kruk, Marek
A1 - Budzynska, Agnieszka
A1 - Goldyn, Ryszard
A1 - Kozak, Anna
A1 - Rosinska, Joanna
A1 - Szelag-Wasielewska, Elzbieta
A1 - Domek, Piotr
A1 - Jakubowska-Krepska, Natalia
A1 - Kwasizur, Kinga
A1 - Messyasz, Beata
A1 - Pelechata, Aleksandra
A1 - Pelechaty, Mariusz
A1 - Kokocinski, Mikolaj
A1 - Madrecka, Beata
A1 - Kostrzewska-Szlakowska, Iwona
A1 - Frak, Magdalena
A1 - Bankowska-Sobczak, Agnieszka
A1 - Wasilewicz, Michal
A1 - Ochocka, Agnieszka
A1 - Pasztaleniec, Agnieszka
A1 - Jasser, Iwona
A1 - Antao-Geraldes, Ana M.
A1 - Leira, Manel
A1 - Hernandez, Armand
A1 - Vasconcelos, Vitor
A1 - Morais, Joao
A1 - Vale, Micaela
A1 - Raposeiro, Pedro M.
A1 - Goncalves, Vitor
A1 - Aleksovski, Boris
A1 - Krstic, Svetislav
A1 - Nemova, Hana
A1 - Drastichova, Iveta
A1 - Chomova, Lucia
A1 - Remec-Rekar, Spela
A1 - Elersek, Tina
A1 - Delgado-Martin, Jordi
A1 - Garcia, David
A1 - Luis Cereijo, Jose
A1 - Goma, Joan
A1 - Carmen Trapote, Mari
A1 - Vegas-Vilarrubia, Teresa
A1 - Obrador, Biel
A1 - Garcia-Murcia, Ana
A1 - Real, Monserrat
A1 - Romans, Elvira
A1 - Noguero-Ribes, Jordi
A1 - Parreno Duque, David
A1 - Fernandez-Moran, Elisabeth
A1 - Ubeda, Barbara
A1 - Angel Galvez, Jose
A1 - Marce, Rafael
A1 - Catalan, Nuria
A1 - Perez-Martinez, Carmen
A1 - Ramos-Rodriguez, Eloisa
A1 - Cillero-Castro, Carmen
A1 - Moreno-Ostos, Enrique
A1 - Maria Blanco, Jose
A1 - Rodriguez, Valeriano
A1 - Juan Montes-Perez, Jorge
A1 - Palomino, Roberto L.
A1 - Rodriguez-Perez, Estela
A1 - Carballeira, Rafael
A1 - Camacho, Antonio
A1 - Picazo, Antonio
A1 - Rochera, Carlos
A1 - Santamans, Anna C.
A1 - Ferriol, Carmen
A1 - Romo, Susana
A1 - Soria, Juan Miguel
A1 - Hansson, Lars-Anders
A1 - Urrutia-Cordero, Pablo
A1 - Ozen, Arda
A1 - Bravo, Andrea G.
A1 - Buck, Moritz
A1 - Colom-Montero, William
A1 - Mustonen, Kristiina
A1 - Pierson, Don
A1 - Yang, Yang
A1 - Verspagen, Jolanda M. H.
A1 - Domis, Lisette N. de Senerpont
A1 - Seelen, Laura
A1 - Teurlincx, Sven
A1 - Verstijnen, Yvon
A1 - Lurling, Miquel
A1 - Maliaka, Valentini
A1 - Faassen, Elisabeth J.
A1 - Latour, Delphine
A1 - Carey, Cayelan C.
A1 - Paerl, Hans W.
A1 - Torokne, Andrea
A1 - Karan, Tunay
A1 - Demir, Nilsun
A1 - Beklioglu, Meryem
A1 - Filiz, Nur
A1 - Levi, Eti E.
A1 - Iskin, Ugur
A1 - Bezirci, Gizem
A1 - Tavsanoglu, Ulku Nihan
A1 - Celik, Kemal
A1 - Ozhan, Koray
A1 - Karakaya, Nusret
A1 - Kocer, Mehmet Ali Turan
A1 - Yilmaz, Mete
A1 - Maraslioglu, Faruk
A1 - Fakioglu, Ozden
A1 - Soylu, Elif Neyran
A1 - Yagci, Meral Apaydin
A1 - Cinar, Sakir
A1 - Capkin, Kadir
A1 - Yagci, Abdulkadir
A1 - Cesur, Mehmet
A1 - Bilgin, Fuat
A1 - Bulut, Cafer
A1 - Uysal, Rahmi
A1 - Koker, Latife
A1 - Akcaalan, Reyhan
A1 - Albay, Meric
A1 - Alp, Mehmet Tahir
A1 - Ozkan, Korhan
A1 - Sevindik, Tugba Ongun
A1 - Tunca, Hatice
A1 - Onem, Burcin
A1 - Richardson, Jessica
A1 - Edwards, Christine
A1 - Bergkemper, Victoria
A1 - Beirne, Eilish
A1 - Cromie, Hannah
A1 - Ibelings, Bastiaan W.
T1 - Data Descriptor: A European Multi Lake Survey dataset of environmental variables, phytoplankton pigments and cyanotoxins
JF - Scientific Data
N2 - Under ongoing climate change and increasing anthropogenic activity, which continuously challenge ecosystem resilience, an in-depth understanding of ecological processes is urgently needed. Lakes, as providers of numerous ecosystem services, face multiple stressors that threaten their functioning. Harmful cyanobacterial blooms are a persistent problem resulting from nutrient pollution and climate-change induced stressors, like poor transparency, increased water temperature and enhanced stratification. Consistency in data collection and analysis methods is necessary to achieve fully comparable datasets and for statistical validity, avoiding issues linked to disparate data sources. The European Multi Lake Survey (EMLS) in summer 2015 was an initiative among scientists from 27 countries to collect and analyse lake physical, chemical and biological variables in a fully standardized manner. This database includes in-situ lake variables along with nutrient, pigment and cyanotoxin data of 369 lakes in Europe, which were centrally analysed in dedicated laboratories. Publishing the EMLS methods and dataset might inspire similar initiatives to study across large geographic areas that will contribute to better understanding lake responses in a changing environment.
KW - Climate-change ecology
KW - Limnology
KW - Water resources
Y1 - 2018
U6 - https://doi.org/10.1038/sdata.2018.226
SN - 2052-4463
VL - 5
PB - Nature Publ. Group
CY - London
ER -
TY - GEN
A1 - Mantzouki, Evanthia
A1 - Lürling, Miquel
A1 - Fastner, Jutta
A1 - Domis, Lisette Nicole de Senerpont
A1 - Wilk-Woźniak, Elżbieta
A1 - Koreiviene, Judita
A1 - Seelen, Laura
A1 - Teurlincx, Sven
A1 - Verstijnen, Yvon
A1 - Krztoń, Wojciech
A1 - Walusiak, Edward
A1 - Karosienė, Jūratė
A1 - Kasperovičienė, Jūratė
A1 - Savadova, Ksenija
A1 - Vitonytė, Irma
A1 - Cillero-Castro, Carmen
A1 - Budzyńska, Agnieszka
A1 - Goldyn, Ryszard
A1 - Kozak, Anna
A1 - Rosińska, Joanna
A1 - Szeląg-Wasielewska, Elżbieta
A1 - Domek, Piotr
A1 - Jakubowska-Krepska, Natalia
A1 - Kwasizur, Kinga
A1 - Messyasz, Beata
A1 - Pełechata, Aleksandra
A1 - Pełechaty, Mariusz
A1 - Kokocinski, Mikolaj
A1 - García-Murcia, Ana
A1 - Real, Monserrat
A1 - Romans, Elvira
A1 - Noguero-Ribes, Jordi
A1 - Duque, David Parreño
A1 - Fernández-Morán, Elísabeth
A1 - Karakaya, Nusret
A1 - Häggqvist, Kerstin
A1 - Beklioğlu, Meryem
A1 - Filiz, Nur
A1 - Levi, Eti E.
A1 - Iskin, Uğur
A1 - Bezirci, Gizem
A1 - Tavşanoğlu, Ülkü Nihan
A1 - Özhan, Koray
A1 - Gkelis, Spyros
A1 - Panou, Manthos
A1 - Fakioglu, Özden
A1 - Avagianos, Christos
A1 - Kaloudis, Triantafyllos
A1 - Çelik, Kemal
A1 - Yilmaz, Mete
A1 - Marcé, Rafael
A1 - Catalán, Nuria
A1 - Bravo, Andrea G.
A1 - Buck, Moritz
A1 - Colom-Montero, William
A1 - Mustonen, Kristiina
A1 - Pierson, Don
A1 - Yang, Yang
A1 - Raposeiro, Pedro M.
A1 - Gonçalves, Vítor
A1 - Antoniou, Maria G.
A1 - Tsiarta, Nikoletta
A1 - McCarthy, Valerie
A1 - Perello, Victor C.
A1 - Feldmann, Tõnu
A1 - Laas, Alo
A1 - Panksep, Kristel
A1 - Tuvikene, Lea
A1 - Gagala, Ilona
A1 - Mankiewicz-Boczek, Joana
A1 - Yağcı, Meral Apaydın
A1 - Çınar, Şakir
A1 - Çapkın, Kadir
A1 - Yağcı, Abdulkadir
A1 - Cesur, Mehmet
A1 - Bilgin, Fuat
A1 - Bulut, Cafer
A1 - Uysal, Rahmi
A1 - Obertegger, Ulrike
A1 - Boscaini, Adriano
A1 - Flaim, Giovanna
A1 - Salmaso, Nico
A1 - Cerasino, Leonardo
A1 - Richardson, Jessica
A1 - Visser, Petra M.
A1 - Verspagen, Jolanda M. H.
A1 - Karan, Tünay
A1 - Soylu, Elif Neyran
A1 - Maraşlıoğlu, Faruk
A1 - Napiórkowska-Krzebietke, Agnieszka
A1 - Ochocka, Agnieszka
A1 - Pasztaleniec, Agnieszka
A1 - Antão-Geraldes, Ana M.
A1 - Vasconcelos, Vitor
A1 - Morais, João
A1 - Vale, Micaela
A1 - Köker, Latife
A1 - Akçaalan, Reyhan
A1 - Albay, Meriç
A1 - Maronić, Dubravka Špoljarić
A1 - Stević, Filip
A1 - Pfeiffer, Tanja Žuna
A1 - Fonvielle, Jeremy Andre
A1 - Straile, Dietmar
A1 - Rothhaupt, Karl-Otto
A1 - Hansson, Lars-Anders
A1 - Urrutia-Cordero, Pablo
A1 - Bláha, Luděk
A1 - Geriš, Rodan
A1 - Fránková, Markéta
A1 - Koçer, Mehmet Ali Turan
A1 - Alp, Mehmet Tahir
A1 - Remec-Rekar, Spela
A1 - Elersek, Tina
A1 - Triantis, Theodoros
A1 - Zervou, Sevasti-Kiriaki
A1 - Hiskia, Anastasia
A1 - Haande, Sigrid
A1 - Skjelbred, Birger
A1 - Madrecka, Beata
A1 - Nemova, Hana
A1 - Drastichova, Iveta
A1 - Chomova, Lucia
A1 - Edwards, Christine
A1 - Sevindik, Tuğba Ongun
A1 - Tunca, Hatice
A1 - Önem, Burçin
A1 - Aleksovski, Boris
A1 - Krstić, Svetislav
A1 - Vucelić, Itana Bokan
A1 - Nawrocka, Lidia
A1 - Salmi, Pauliina
A1 - Machado-Vieira, Danielle
A1 - Oliveira, Alinne Gurjão De
A1 - Delgado-Martín, Jordi
A1 - García, David
A1 - Cereijo, Jose Luís
A1 - Gomà, Joan
A1 - Trapote, Mari Carmen
A1 - Vegas-Vilarrúbia, Teresa
A1 - Obrador, Biel
A1 - Grabowska, Magdalena
A1 - Karpowicz, Maciej
A1 - Chmura, Damian
A1 - Úbeda, Bárbara
A1 - Gálvez, José Ángel
A1 - Özen, Arda
A1 - Christoffersen, Kirsten Seestern
A1 - Warming, Trine Perlt
A1 - Kobos, Justyna
A1 - Mazur-Marzec, Hanna
A1 - Pérez-Martínez, Carmen
A1 - Ramos-Rodríguez, Eloísa
A1 - Arvola, Lauri
A1 - Alcaraz-Párraga, Pablo
A1 - Toporowska, Magdalena
A1 - Pawlik-Skowronska, Barbara
A1 - Niedźwiecki, Michał
A1 - Pęczuła, Wojciech
A1 - Leira, Manel
A1 - Hernández, Armand
A1 - Moreno-Ostos, Enrique
A1 - Blanco, José María
A1 - Rodríguez, Valeriano
A1 - Montes-Pérez, Jorge Juan
A1 - Palomino, Roberto L.
A1 - Rodríguez-Pérez, Estela
A1 - Carballeira, Rafael
A1 - Camacho, Antonio
A1 - Picazo, Antonio
A1 - Rochera, Carlos
A1 - Santamans, Anna C.
A1 - Ferriol, Carmen
A1 - Romo, Susana
A1 - Soria, Juan Miguel
A1 - Dunalska, Julita
A1 - Sieńska, Justyna
A1 - Szymański, Daniel
A1 - Kruk, Marek
A1 - Kostrzewska-Szlakowska, Iwona
A1 - Jasser, Iwona
A1 - Žutinić, Petar
A1 - Udovič, Marija Gligora
A1 - Plenković-Moraj, Anđelka
A1 - Frąk, Magdalena
A1 - Bańkowska-Sobczak, Agnieszka
A1 - Wasilewicz, Michał
A1 - Özkan, Korhan
A1 - Maliaka, Valentini
A1 - Kangro, Kersti
A1 - Grossart, Hans-Peter
A1 - Paerl, Hans W.
A1 - Carey, Cayelan C.
A1 - Ibelings, Bas W.
T1 - Temperature effects explain continental scale distribution of cyanobacterial toxins
T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2 - Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a) and cytotoxins (e.g., cylindrospermopsin) due to their potency. Most studies examine the relationship between individual toxin variants and environmental factors, such as nutrients, temperature and light. In summer 2015, we collected samples across Europe to investigate the effect of nutrient and temperature gradients on the variability of toxin production at a continental scale. Direct and indirect effects of temperature were the main drivers of the spatial distribution in the toxins produced by the cyanobacterial community, the toxin concentrations and toxin quota. Generalized linear models showed that a Toxin Diversity Index (TDI) increased with latitude, while it decreased with water stability. Increases in TDI were explained through a significant increase in toxin variants such as MC-YR, anatoxin and cylindrospermopsin, accompanied by a decreasing presence of MC-LR. While global warming continues, the direct and indirect effects of increased lake temperatures will drive changes in the distribution of cyanobacterial toxins in Europe, potentially promoting selection of a few highly toxic species or strains.
T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1105
KW - microcystin
KW - anatoxin
KW - cylindrospermopsin
KW - temperature
KW - direct effects
KW - indirect effects
KW - spatial distribution
KW - European Multi Lake Survey
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-427902
SN - 1866-8372
IS - 1105
ER -
TY - JOUR
A1 - Henkel, Janin
A1 - Coleman, Charles Dominic
A1 - Schraplau, Anne
A1 - Jöhrens, Korinna
A1 - Weber, Daniela
A1 - Castro, Jose Pedro
A1 - Hugo, Martin
A1 - Schulz, Tim Julius
A1 - Krämer, Stephanie
A1 - Schürmann, Annette
A1 - Püschel, Gerhard Paul
T1 - Induction of Steatohepatitis (NASH) with Insulin Resistance in Wild-type B6 Mice by a Western-type Diet Containing Soybean Oil and Cholesterol
JF - Molecular medicine
N2 - Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are hepatic manifestations of the metabolic syndrome. Many currently used animal models of NAFLD/NASH lack clinical features of either NASH or metabolic syndrome such as hepatic inflammation and fibrosis (e.g., high-fat diets) or overweight and insulin resistance (e.g., methionine-choline-deficient diets), or they are based on monogenetic defects (e.g., ob/ob mice). In the current study, a Western-type diet containing soybean oil with high n-6-PUFA and 0.75% cholesterol (SOD + Cho) induced steatosis, inflammation and fibrosis accompanied by hepatic lipid peroxidation and oxidative stress in livers of C57BL/6-mice, which in addition showed increased weight gain and insulin resistance, thus displaying a phenotype closely resembling all clinical features of NASH in patients with metabolic syndrome. In striking contrast, a soybean oil-containing Western-type diet without cholesterol (SOD) induced only mild steatosis but not hepatic inflammation, fibrosis, weight gain or insulin resistance. Another high-fat diet, mainly consisting of lard and supplemented with fructose in drinking water (LAD + Fru), resulted in more prominent weight gain, insulin resistance and hepatic steatosis than SOD + Cho, but livers were devoid of inflammation and fibrosis. Although both LAD + Fru-and SOD + Cho-fed animals had high plasma cholesterol, liver cholesterol was elevated only in SOD + Cho animals. Cholesterol induced expression of chemotactic and inflammatory cytokines in cultured Kupffer cells and rendered hepatocytes more susceptible to apoptosis. In summary, dietary cholesterol in the SOD + Cho diet may trigger hepatic inflammation and fibrosis. SOD + Cho-fed animals may be a useful disease model displaying many clinical features of patients with the metabolic syndrome and NASH.
KW - Nonalcoholic Steatohepatitis (NASH)
KW - Typical Western Diet
KW - Nonalcoholic Fatty Liver Disease (NAFLD)
KW - Dietary Cholesterol
KW - Kupffer Cells
Y1 - 2017
U6 - https://doi.org/10.2119/molmed.2016.00203
SN - 1076-1551
SN - 1528-3658
VL - 23
SP - 70
EP - 82
PB - Feinstein Inst. for Medical Research
CY - Manhasset
ER -
TY - GEN
A1 - Henkel, Janin
A1 - Buchheim-Dieckow, Katja
A1 - Castro, José Pedro
A1 - Laeger, Thomas
A1 - Wardelmann, Kristina
A1 - Kleinridders, André
A1 - Jöhrens, Korinna
A1 - Püschel, Gerhard Paul
T1 - Reduced Oxidative Stress and Enhanced FGF21 Formation in Livers of Endurance-Exercised Rats with Diet-Induced NASH
T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2 - Non-alcoholic fatty liver diseases (NAFLD) including the severe form with steatohepatitis (NASH) are highly prevalent ailments to which no approved pharmacological treatment exists. Dietary intervention aiming at 10% weight reduction is efficient but fails due to low compliance. Increase in physical activity is an alternative that improved NAFLD even in the absence of weight reduction. The underlying mechanisms are unclear and cannot be studied in humans. Here, a rat NAFLD model was developed that reproduces many facets of the diet-induced NAFLD in humans. The impact of endurance exercise was studied in this model. Male Wistar rats received control chow or a NASH-inducing diet rich in fat, cholesterol, and fructose. Both diet groups were subdivided into a sedentary and an endurance exercise group. Animals receiving the NASH-inducing diet gained more body weight, got glucose intolerant and developed a liver pathology with steatosis, hepatocyte hypertrophy, inflammation and fibrosis typical of NAFLD or NASH. Contrary to expectations, endurance exercise did not improve the NASH activity score and even enhanced hepatic inflammation. However, endurance exercise attenuated the hepatic cholesterol overload and the ensuing severe oxidative stress. In addition, exercise improved glucose tolerance possibly in part by induction of hepatic FGF21 production.
T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 807
KW - NAFLD
KW - NASH
KW - endurance exercise
KW - FGF21
KW - glucose intolerance
KW - cholesterol
KW - oxidative stress
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-442384
SN - 1866-8372
IS - 807
ER -
TY - JOUR
A1 - Henkel, Janin
A1 - Buchheim-Dieckow, Katja
A1 - Castro, José Pedro
A1 - Laeger, Thomas
A1 - Wardelmann, Kristina
A1 - Kleinridders, André
A1 - Jöhrens, Korinna
A1 - Püschel, Gerhard Paul
T1 - Reduced Oxidative Stress and Enhanced FGF21 Formation in Livers of Endurance-Exercised Rats with Diet-Induced NASH
JF - Nutrients
N2 - Non-alcoholic fatty liver diseases (NAFLD) including the severe form with steatohepatitis (NASH) are highly prevalent ailments to which no approved pharmacological treatment exists. Dietary intervention aiming at 10% weight reduction is efficient but fails due to low compliance. Increase in physical activity is an alternative that improved NAFLD even in the absence of weight reduction. The underlying mechanisms are unclear and cannot be studied in humans. Here, a rat NAFLD model was developed that reproduces many facets of the diet-induced NAFLD in humans. The impact of endurance exercise was studied in this model. Male Wistar rats received control chow or a NASH-inducing diet rich in fat, cholesterol, and fructose. Both diet groups were subdivided into a sedentary and an endurance exercise group. Animals receiving the NASH-inducing diet gained more body weight, got glucose intolerant and developed a liver pathology with steatosis, hepatocyte hypertrophy, inflammation and fibrosis typical of NAFLD or NASH. Contrary to expectations, endurance exercise did not improve the NASH activity score and even enhanced hepatic inflammation. However, endurance exercise attenuated the hepatic cholesterol overload and the ensuing severe oxidative stress. In addition, exercise improved glucose tolerance possibly in part by induction of hepatic FGF21 production.
KW - NAFLD
KW - NASH
KW - endurance exercise
KW - FGF21
KW - glucose intolerance
KW - cholesterol
KW - oxidative stress
Y1 - 2019
U6 - https://doi.org/10.3390/nu11112709
SN - 2072-6643
VL - 11
IS - 11
PB - MDPI
CY - Basel
ER -
TY - JOUR
A1 - Henkel, Janin
A1 - Alfine, Eugenia
A1 - Saín, Juliana
A1 - Jöhrens, Korinna
A1 - Weber, Daniela
A1 - Castro, José Pedro
A1 - König, Jeannette
A1 - Stuhlmann, Christin
A1 - Vahrenbrink, Madita
A1 - Jonas, Wenke
A1 - Kleinridders, André
A1 - Püschel, Gerhard Paul
T1 - Soybean Oil-Derived Poly-Unsaturated Fatty Acids Enhance Liver Damage in NAFLD Induced by Dietary Cholesterol
JF - Nutrients
N2 - While the impact of dietary cholesterol on the progression of atherosclerosis has probably been overestimated, increasing evidence suggests that dietary cholesterol might favor the transition from blunt steatosis to non-alcoholic steatohepatitis (NASH), especially in combination with high fat diets. It is poorly understood how cholesterol alone or in combination with other dietary lipid components contributes to the development of lipotoxicity. The current study demonstrated that liver damage caused by dietary cholesterol in mice was strongly enhanced by a high fat diet containing soybean oil-derived ω6-poly-unsaturated fatty acids (ω6-PUFA), but not by a lard-based high fat diet containing mainly saturated fatty acids. In contrast to the lard-based diet the soybean oil-based diet augmented cholesterol accumulation in hepatocytes, presumably by impairing cholesterol-eliminating pathways. The soybean oil-based diet enhanced cholesterol-induced mitochondrial damage and amplified the ensuing oxidative stress, probably by peroxidation of poly-unsaturated fatty acids. This resulted in hepatocyte death, recruitment of inflammatory cells, and fibrosis, and caused a transition from steatosis to NASH, doubling the NASH activity score. Thus, the recommendation to reduce cholesterol intake, in particular in diets rich in ω6-PUFA, although not necessary to reduce the risk of atherosclerosis, might be sensible for patients suffering from non-alcoholic fatty liver disease.
KW - non-alcoholic fatty liver disease (NAFLD)
KW - NASH
KW - cholesterol
KW - PUFA
KW - inflammation
KW - oxidative stress
Y1 - 2018
U6 - https://doi.org/10.3390/nu10091326
SN - 2072-6643
VL - 10
IS - 9
SP - 1
EP - 17
PB - Molecular Diversity Preservation International (MDPI)
CY - Basel
ER -
TY - GEN
A1 - Henkel, Janin
A1 - Alfine, Eugenia
A1 - Saín, Juliana
A1 - Jöhrens, Korinna
A1 - Weber, Daniela
A1 - Castro, José Pedro
A1 - König, Jeannette
A1 - Stuhlmann, Christin
A1 - Vahrenbrink, Madita
A1 - Jonas, Wenke
A1 - Kleinridders, André
A1 - Püschel, Gerhard Paul
T1 - Soybean Oil-Derived Poly-Unsaturated Fatty Acids Enhance Liver Damage in NAFLD Induced by Dietary Cholesterol
T2 - Nutrients
N2 - While the impact of dietary cholesterol on the progression of atherosclerosis has probably been overestimated, increasing evidence suggests that dietary cholesterol might favor the transition from blunt steatosis to non-alcoholic steatohepatitis (NASH), especially in combination with high fat diets. It is poorly understood how cholesterol alone or in combination with other dietary lipid components contributes to the development of lipotoxicity. The current study demonstrated that liver damage caused by dietary cholesterol in mice was strongly enhanced by a high fat diet containing soybean oil-derived ω6-poly-unsaturated fatty acids (ω6-PUFA), but not by a lard-based high fat diet containing mainly saturated fatty acids. In contrast to the lard-based diet the soybean oil-based diet augmented cholesterol accumulation in hepatocytes, presumably by impairing cholesterol-eliminating pathways. The soybean oil-based diet enhanced cholesterol-induced mitochondrial damage and amplified the ensuing oxidative stress, probably by peroxidation of poly-unsaturated fatty acids. This resulted in hepatocyte death, recruitment of inflammatory cells, and fibrosis, and caused a transition from steatosis to NASH, doubling the NASH activity score. Thus, the recommendation to reduce cholesterol intake, in particular in diets rich in ω6-PUFA, although not necessary to reduce the risk of atherosclerosis, might be sensible for patients suffering from non-alcoholic fatty liver disease.
T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 479
KW - non-alcoholic fatty liver disease (NAFLD)
KW - NASH
KW - cholesterol
KW - PUFA
KW - inflammation
KW - oxidative stress
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-419773
ER -
TY - GEN
A1 - Wardelmann, Kristina
A1 - Rath, Michaela
A1 - Castro, José Pedro
A1 - Blümel, Sabine
A1 - Schell, Mareike
A1 - Hauffe, Robert
A1 - Schumacher, Fabian
A1 - Flore, Tanina
A1 - Ritter, Katrin
A1 - Wernitz, Andreas
A1 - Hosoi, Toru
A1 - Ozawa, Koichiro
A1 - Kleuser, Burkhard
A1 - Weiß, Jürgen
A1 - Schürmann, Annette
A1 - Kleinridders, André
T1 - Central acting Hsp10 regulates mitochondrial function, fatty acid metabolism and insulin sensitivity in the hypothalamus
T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2 - Mitochondria are critical for hypothalamic function and regulators of metabolism. Hypothalamic mitochondrial dysfunction with decreased mitochondrial chaperone expression is present in type 2 diabetes (T2D). Recently, we demonstrated that a dysregulated mitochondrial stress response (MSR) with reduced chaperone expression in the hypothalamus is an early event in obesity development due to insufficient insulin signaling. Although insulin activates this response and improves metabolism, the metabolic impact of one of its members, the mitochondrial chaperone heat shock protein 10 (Hsp10), is unknown. Thus, we hypothesized that a reduction of Hsp10 in hypothalamic neurons will impair mitochondrial function and impact brain insulin action. Therefore, we investigated the role of chaperone Hsp10 by introducing a lentiviral-mediated Hsp10 knockdown (KD) in the hypothalamic cell line CLU-183 and in the arcuate nucleus (ARC) of C57BL/6N male mice. We analyzed mitochondrial function and insulin signaling utilizing qPCR, Western blot, XF96 Analyzer, immunohistochemistry, and microscopy techniques. We show that Hsp10 expression is reduced in T2D mice brains and regulated by leptin in vitro. Hsp10 KD in hypothalamic cells induced mitochondrial dysfunction with altered fatty acid metabolism and increased mitochondria-specific oxidative stress resulting in neuronal insulin resistance. Consequently, the reduction of Hsp10 in the ARC of C57BL/6N mice caused hypothalamic insulin resistance with acute liver insulin resistance.
T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1165
KW - brain insulin signaling
KW - mitochondria
KW - oxidative stress
KW - fatty acid metabolism
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-522985
SN - 1866-8372
IS - 5
ER -
TY - JOUR
A1 - Wardelmann, Kristina
A1 - Rath, Michaela
A1 - Castro, José Pedro
A1 - Blümel, Sabine
A1 - Schell, Mareike
A1 - Hauffe, Robert
A1 - Schumacher, Fabian
A1 - Flore, Tanina
A1 - Ritter, Katrin
A1 - Wernitz, Andreas
A1 - Hosoi, Toru
A1 - Ozawa, Koichiro
A1 - Kleuser, Burkhard
A1 - Weiß, Jürgen
A1 - Schürmann, Annette
A1 - Kleinridders, André
T1 - Central acting Hsp10 regulates mitochondrial function, fatty acid metabolism and insulin sensitivity in the hypothalamus
JF - Antioxidants
N2 - Mitochondria are critical for hypothalamic function and regulators of metabolism. Hypothalamic mitochondrial dysfunction with decreased mitochondrial chaperone expression is present in type 2 diabetes (T2D). Recently, we demonstrated that a dysregulated mitochondrial stress response (MSR) with reduced chaperone expression in the hypothalamus is an early event in obesity development due to insufficient insulin signaling. Although insulin activates this response and improves metabolism, the metabolic impact of one of its members, the mitochondrial chaperone heat shock protein 10 (Hsp10), is unknown. Thus, we hypothesized that a reduction of Hsp10 in hypothalamic neurons will impair mitochondrial function and impact brain insulin action. Therefore, we investigated the role of chaperone Hsp10 by introducing a lentiviral-mediated Hsp10 knockdown (KD) in the hypothalamic cell line CLU-183 and in the arcuate nucleus (ARC) of C57BL/6N male mice. We analyzed mitochondrial function and insulin signaling utilizing qPCR, Western blot, XF96 Analyzer, immunohistochemistry, and microscopy techniques. We show that Hsp10 expression is reduced in T2D mice brains and regulated by leptin in vitro. Hsp10 KD in hypothalamic cells induced mitochondrial dysfunction with altered fatty acid metabolism and increased mitochondria-specific oxidative stress resulting in neuronal insulin resistance. Consequently, the reduction of Hsp10 in the ARC of C57BL/6N mice caused hypothalamic insulin resistance with acute liver insulin resistance.
KW - brain insulin signaling
KW - mitochondria
KW - oxidative stress
KW - fatty acid metabolism
Y1 - 2021
U6 - https://doi.org/10.3390/antiox10050711
SN - 2076-3921
VL - 10
IS - 5
PB - MDPI
CY - Basel
ER -
TY - GEN
A1 - Castro, José Pedro
A1 - Grune, Tilman
A1 - Speckmann, Bodo
T1 - The two faces of reactive oxygen species (ROS) in adipocyte function and dysfunction
N2 - White adipose tissue (WAT) is actively involved in the regulation of whole-body energy homeostasis via storage/release of lipids and adipokine secretion. Current research links WAT dysfunction to the development of metabolic syndrome (MetS) and type 2 diabetes (T2D). The expansion of WAT during oversupply of nutrients prevents ectopic fat accumulation and requires proper preadipocyte-to-adipocyte differentiation. An assumed link between excess levels of reactive oxygen species (ROS), WAT dysfunction and T2D has been discussed controversially. While oxidative stress conditions have conclusively been detected in WAT of T2D patients and related animal models, clinical trials with antioxidants failed to prevent T2D or to improve glucose homeostasis. Furthermore, animal studies yielded inconsistent results regarding the role of oxidative stress in the development of diabetes. Here, we discuss the contribution of ROS to the (patho)physiology of adipocyte function and differentiation, with particular emphasis on sources and nutritional modulators of adipocyte ROS and their functions in signaling mechanisms controlling adipogenesis and functions of mature fat cells. We propose a concept of ROS balance that is required for normal functioning of WAT. We explain how both excessive and diminished levels of ROS, e.g. resulting from over supplementation with antioxidants, contribute to WAT dysfunction and subsequently insulin resistance.
T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 339
KW - adipogenesis
KW - adipose tissue dysregulation
KW - antioxidants
KW - metabolic disorders
KW - oxidative stress
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-398039
ER -
TY - GEN
A1 - Castro, José Pedro
A1 - Wardelmann, Kristina
A1 - Grune, Tilman
A1 - Kleinridders, André
T1 - Mitochondrial chaperones in the brain
BT - safeguarding brain health and metabolism?
T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2 - The brain orchestrates organ function and regulates whole body metabolism by the concerted action of neurons and glia cells in the central nervous system. To do so, the brain has tremendously high energy consumption and relies mainly on glucose utilization and mitochondrial function in order to exert its function. As a consequence of high rate metabolism, mitochondria in the brain accumulate errors over time, such as mitochondrial DNA (mtDNA) mutations, reactive oxygen species, and misfolded and aggregated proteins. Thus, mitochondria need to employ specific mechanisms to avoid or ameliorate the rise of damaged proteins that contribute to aberrant mitochondrial function and oxidative stress. To maintain mitochondria homeostasis (mitostasis), cells evolved molecular chaperones that shuttle, refold, or in coordination with proteolytic systems, help to maintain a low steady-state level of misfolded/aggregated proteins. Their importance is exemplified by the occurrence of various brain diseases which exhibit reduced action of chaperones. Chaperone loss (expression and/or function) has been observed during aging, metabolic diseases such as type 2 diabetes and in neurode-generative diseases such as Alzheimer's (AD), Parkinson's (PD) or even Huntington's (HD) diseases, where the accumulation of damage proteins is evidenced. Within this perspective, we propose that proper brain function is maintained by the joint action of mitochondrial chaperones to ensure and maintain mitostasis contributing to brain health, and that upon failure, alter brain function which can cause metabolic diseases.
T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1031
KW - insulin signaling
KW - brain
KW - chaperones
KW - mitochondria homeostasis
KW - mitochondrial dysfunction
KW - neurodegeneration
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-460650
SN - 1866-8372
IS - 1031
ER -
TY - JOUR
A1 - Reeg, Sandra
A1 - Jung, Tobias
A1 - Castro, José Pedro
A1 - Davies, Kelvin J. A.
A1 - Henze, Andrea
A1 - Grune, Tilman
T1 - The molecular chaperone Hsp70 promotes the proteolytic removal of oxidatively damaged proteins by the proteasome
JF - Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research
N2 - One hallmark of aging is the accumulation of protein aggregates, promoted by the unfolding of oxidized proteins. Unraveling the mechanism by which oxidized proteins are degraded may provide a basis to delay the early onset of features, such as protein aggregate formation, that contribute to the aging phenotype. In order to prevent aggregation of oxidized proteins, cells recur to the 20S proteasome, an efficient turnover proteolysis complex. It has previously been shown that upon oxidative stress the 26S proteasome, another form, dissociates into the 20S form. A critical player implicated in its dissociation is the Heat Shock Protein 70 (Hsp70), which promotes an increase in free 20S proteasome and, therefore, an increased capability to degrade oxidized proteins. The aim of this study was to test whether or not Hsp70 is involved in cooperating with the 20S proteasome for a selective degradation of oxidatively damaged proteins. Our results demonstrate that Hsp70 expression is induced in HT22 cells as a result of mild oxidative stress conditions. Furthermore, Hsp70 prevents the accumulation of oxidized proteins and directly promotes their degradation by the 20S proteasome. In contrast the expression of the Heat shock cognate protein 70 (Hsc70) was not changed in recovery after oxidative stress and Hsc70 has no influence on the removal of oxidatively damaged proteins. We were able to demonstrate in HT22 cells, in brain homogenates from 129/SV mice and in vitro, that there is an increased interaction of Hsp70 with oxidized proteins, but also with the 20S proteasome, indicating a role of Hsp70 in mediating the interaction of oxidized proteins with the 20S proteasome. Thus, our data clearly implicate an involvement of Hsp70 oxidatively damaged protein degradation by the 20S proteasome. c) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
KW - Protein oxidation
KW - Proteasome
KW - Chaperone
KW - HSP70
Y1 - 2016
U6 - https://doi.org/10.1016/j.freeradbiomed.2016.08.002
SN - 0891-5849
SN - 1873-4596
VL - 99
SP - 153
EP - 166
PB - Elsevier
CY - New York
ER -
TY - JOUR
A1 - Castro, José Pedro
A1 - Grune, Tilman
A1 - Speckmann, Bodo
T1 - The two faces of reactive oxygen species (ROS) in adipocyte function and dysfunction
JF - Biological chemistry
N2 - White adipose tissue (WAT) is actively involved in the regulation of whole-body energy homeostasis via storage/ release of lipids and adipokine secretion. Current research links WAT dysfunction to the development of metabolic syndrome (MetS) and type 2 diabetes (T2D). The expansion of WAT during oversupply of nutrients prevents ectopic fat accumulation and requires proper preadipocyte-to-adipocyte differentiation. An assumed link between excess levels of reactive oxygen species (ROS), WAT dysfunction and T2D has been discussed controversially. While oxidative stress conditions have conclusively been detected in WAT of T2D patients and related animal models, clinical trials with antioxidants failed to prevent T2D or to improve glucose homeostasis. Furthermore, animal studies yielded inconsistent results regarding the role of oxidative stress in the development of diabetes. Here, we discuss the contribution of ROS to the (patho) physiology of adipocyte function and differentiation, with particular emphasis on sources and nutritional modulators of adipocyte ROS and their functions in signaling mechanisms controlling adipogenesis and functions of mature fat cells. We propose a concept of ROS balance that is required for normal functioning of WAT. We explain how both excessive and diminished levels of ROS, e. g. resulting from over supplementation with antioxidants, contribute to WAT dysfunction and subsequently insulin resistance.
KW - adipogenesis
KW - adipose tissue dysregulation
KW - antioxidants
KW - metabolic disorders
KW - oxidative stress
Y1 - 2016
U6 - https://doi.org/10.1515/hsz-2015-0305
SN - 1431-6730
SN - 1437-4315
VL - 397
SP - 709
EP - 724
PB - De Gruyter
CY - Berlin
ER -
TY - JOUR
A1 - Fernando, Raquel
A1 - Drescher, Cathleen
A1 - Nowotny, Kerstin
A1 - Grune, Tilman
A1 - Castro, Jose Pedro
T1 - Impaired proteostasis during skeletal muscle aging
JF - Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research
N2 - Aging is a complex phenomenon that has detrimental effects on tissue homeostasis. The skeletal muscle is one of the earliest tissues to be affected and to manifest age-related changes such as functional impairment and the loss of mass. Common to these alterations and to most of tissues during aging is the disruption of the proteostasis network by detrimental changes in the ubiquitin-proteasomal system (UPS) and the autophagy-lysosomal system (ALS). In fact, during aging the accumulation of protein aggregates, a process mainly driven by increased levels of oxidative stress, has been observed, clearly demonstrating UPS and ALS dysregulation. Since the UPS and ALS are the two most important pathways for the removal of misfolded and aggregated proteins and also of damaged organelles, we provide here an overview on the current knowledge regarding the connection between the loss of proteostasis and skeletal muscle functional impairment and also how redox regulation can play a role during aging. Therefore, this review serves for a better understanding of skeletal muscle aging in regard to the loss of proteostasis and how redox regulation can impact its function and maintenance.
KW - Skeletal muscle
KW - Proteostasis
KW - Proteasome and lysosome
KW - Oxidative stress
KW - Redox regulation
KW - Aging
Y1 - 2018
U6 - https://doi.org/10.1016/j.freeradbiomed.2018.08.037
SN - 0891-5849
SN - 1873-4596
VL - 132
SP - 58
EP - 66
PB - Elsevier
CY - New York
ER -
TY - JOUR
A1 - Fernando, Raquel
A1 - Drescher, Cathleen
A1 - Deubel, Stefanie
A1 - Jung, Tobias
A1 - Ost, Mario
A1 - Klaus, Susanne
A1 - Grune, Tilman
A1 - Castro, Jose Pedro
T1 - Low proteasomal activity in fast skeletal muscle fibers is not associated with increased age-related oxidative damage
JF - Experimental gerontology
N2 - The skeletal muscle is a crucial tissue for maintaining whole body homeostasis. Aging seems to have a disruptive effect on skeletal muscle homeostasis including proteostasis. However, how aging specifically impacts slow and fast twitch fiber types remains elusive. Muscle proteostasis is largely maintained by the proteasomal system. Here we characterized the proteasomal system in two different fiber types, using a non-sarcopenic aging model. By analyzing the proteasomal activity and amount, as well as the polyubiquitinated proteins and the level of protein oxidation in Musculus soleus (Sol) and Musculus extensor digitorum longus (EDL), we found that the slow twitch Sol muscle shows an overall higher respiratory and proteasomal activity in young and old animals. However, especially during aging the fast twitch EDL muscle reduces protein oxidation by an increase of antioxidant capacity. Thus, under adaptive non-sarcopenic conditions, the two fibers types seem to have different strategies to avoid age-related changes.
KW - Proteasomal system
KW - Skeletal muscle
KW - Fast and slow fibers
KW - Polyubiquitination
KW - Oxidized proteins
KW - Antioxidants
KW - Aging
KW - Mitochondrial respiration
Y1 - 2018
U6 - https://doi.org/10.1016/j.exger.2018.10.018
SN - 0531-5565
SN - 1873-6815
VL - 117
SP - 45
EP - 52
PB - Elsevier
CY - Oxford
ER -
TY - JOUR
A1 - Castro, Jose Pedro
A1 - Fernando, Raquel
A1 - Reeg, Sandra
A1 - Meinl, Walter
A1 - Almeida, Henrique
A1 - Grune, Tilman
T1 - Non-enzymatic cleavage of Hsp90 by oxidative stress leads to actin aggregate formation
BT - A novel gain-of-function mechanism
JF - Redox Biology
N2 - Aging is accompanied by the accumulation of oxidized proteins. To remove them, cells employ the proteasomal and autophagy-lysosomal systems; however, if the clearance rate is inferior to its formation, protein aggregates form as a hallmark of proteostasis loss. In cells, during stress conditions, actin aggregates accumulate leading to impaired proliferation and reduced proteasomal activity, as observed in cellular senescence. The heat shock protein 90 (Hsp90) is a molecular chaperone that binds and protects the proteasome from oxidative inactivation. We hypothesized that in oxidative stress conditions a malfunction of Hsp90 occurs resulting in the aforementioned protein aggregates. Here, we demonstrate that upon oxidative stress Hsp90 loses its function in a highly specific non-enzymatic iron-catalyzed oxidation event and its breakdown product, a cleaved form of Hsp90 (Hsp90cl), acquires a new function in mediating the accumulation of actin aggregates. Moreover, the prevention of Hsp90 cleavage reduces oxidized actin accumulation, whereas transfection of the cleaved form of Hsp90 leads to an enhanced accumulation of oxidized actin. This indicates a clear role of the Hsp90cl in the aggregation of oxidized proteins.
KW - Oxidative stress
KW - Protein oxidation
KW - Heat shock protein 90
KW - Proteasome
KW - Protein aggregates
Y1 - 2019
U6 - https://doi.org/10.1016/j.redox.2019.101108
SN - 2213-2317
VL - 21
PB - Elsevier
CY - Amsterdam
ER -
TY - JOUR
A1 - Castro, Jose Pedro
A1 - Wardelmann, Kristina
A1 - Grune, Tilman
A1 - Kleinridders, Andre
T1 - Mitochondrial Chaperones in the Brain
BT - safeguarding Brain Health and Metabolism?
JF - Frontiers in Endocrinology
N2 - The brain orchestrates organ function and regulates whole body metabolism by the concerted action of neurons and glia cells in the central nervous system. To do so, the brain has tremendously high energy consumption and relies mainly on glucose utilization and mitochondrial function in order to exert its function. As a consequence of high rate metabolism, mitochondria in the brain accumulate errors over time, such as mitochondrial DNA (mtDNA) mutations, reactive oxygen species, and misfolded and aggregated proteins. Thus, mitochondria need to employ specific mechanisms to avoid or ameliorate the rise of damaged proteins that contribute to aberrant mitochondrial function and oxidative stress. To maintain mitochondria homeostasis (mitostasis), cells evolved molecular chaperones that shuttle, refold, or in coordination with proteolytic systems, help to maintain a low steady-state level of misfolded/aggregated proteins. Their importance is exemplified by the occurrence of various brain diseases which exhibit reduced action of chaperones. Chaperone loss (expression and/or function) has been observed during aging, metabolic diseases such as type 2 diabetes and in neurode-generative diseases such as Alzheimer's (AD), Parkinson's (PD) or even Huntington's (HD) diseases, where the accumulation of damage proteins is evidenced. Within this perspective, we propose that proper brain function is maintained by the joint action of mitochondrial chaperones to ensure and maintain mitostasis contributing to brain health, and that upon failure, alter brain function which can cause metabolic diseases.
KW - insulin signaling
KW - brain
KW - chaperones
KW - mitochondria homeostasis
KW - mitochondrial dysfunction
KW - neurodegeneration
Y1 - 2018
U6 - https://doi.org/10.3389/fendo.2018.00196
SN - 1664-2392
VL - 9
PB - Frontiers Research Foundation
CY - Lausanne
ER -
TY - JOUR
A1 - Nowotny, Kerstin
A1 - Castro, Jose Pedro
A1 - Hugo, Martin
A1 - Braune, Sabine
A1 - Weber, Daniela
A1 - Pignitter, Marc
A1 - Somoza, Veronika
A1 - Bornhorst, Julia
A1 - Schwerdtle, Tanja
A1 - Grune, Tilman
T1 - Oxidants produced by methylglyoxal-modified collagen trigger ER stress and apoptosis in skin fibroblasts
JF - Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research
N2 - Methylglyoxal (MG), a highly reactive dicarbonyl, interacts with proteins to form advanced glycation end products (AGEs). AGEs include a variety of compounds which were shown to have damaging potential and to accumulate in the course of different conditions such as diabetes mellitus and aging. After confirming collagen as a main target for MG modifications in vivo within the extracellular matrix, we show here that MG-collagen disrupts fibroblast redox homeostasis and induces endoplasmic reticulum (ER) stress and apoptosis. In particular, MG-collagen-induced apoptosis is associated with the activation of the PERK-eIF2 alpha pathway and caspase-12. MG-collagen contributes to altered redox homeostasis by directly generating hydrogen peroxide and oxygen-derived free radicals. The induction of ER stress in human fibroblasts was confirmed using collagen extracts isolated from old mice in which MG-derived AGEs were enriched. In conclusion, MG-derived AGEs represent one factor contributing to diminished fibroblast function during aging.
KW - Advanced glycation end products
KW - Aging
KW - Apoptosis
KW - Collagen
KW - ER stress
KW - Methylglyoxal
KW - Redox homeostasis
Y1 - 2018
U6 - https://doi.org/10.1016/j.freeradbiomed.2018.03.022
SN - 0891-5849
SN - 1873-4596
VL - 120
SP - 102
EP - 113
PB - Elsevier
CY - New York
ER -
TY - GEN
A1 - Fernando, Raquel
A1 - Drescher, Cathleen
A1 - Deubel, Stefanie
A1 - Grune, Tilman
A1 - Castro, Jose Pedro
T1 - Distinct proteasomal activity for fast and slow twitch skeletal muscle during aging
T2 - Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research
N2 - Skeletal muscle alterations during aging lead to dysfunctional metabolism, correlating with frailty and early mortality. The loss of proteostasis is a hallmark of aging. Whether proteostasis loss plays a role in muscle aging remains elusive. To address this question we collected muscles, Soleus (SOL, type I) and Extensor digitorum longus (EDL, type II), from young (4 months) and old (25 months) C57BL/6 mice and evaluated the proteasomal system. Initial work showed decreased 26 S activity in old SOL. EDL displayed lower proteasomal activity in both ages compared to any of the SOL ages. Moreover, in order to understand if during aging there is the so-called “fiber switch from fast-to-slow”, we performed western blots against sMHC and fMHC (slow and fast myosin heavy chain, respectively). Preliminary results suggest that young SOL is composed by slow twitch fibers but also contains fast twitch fibers, while young EDL seems to be mostly composed by fast twitch fibers that level down during aging, suggesting the switch. As a conclusion, EDL seems to have less proteasomal activity, however, if this is a contributor or a consequence to the muscle fiber switch during aging still needs further investigation.
Y1 - 2018
U6 - https://doi.org/10.1016/j.freeradbiomed.2018.04.393
SN - 0891-5849
SN - 1873-4596
VL - 120
SP - S119
EP - S119
PB - Elsevier
CY - New York
ER -
TY - JOUR
A1 - Wiedmer, Petra
A1 - Jung, Tobias
A1 - Castro, Jose Pedro
A1 - Pomatto, Laura C. D.
A1 - Sun, Patrick Y.
A1 - Davies, Kelvin J. A.
A1 - Grune, Tilman
T1 - Sarcopenia
BT - molecular mechanisms and open questions
JF - Ageing research reviews : ARR
N2 - Sarcopenia represents a muscle-wasting syndrome characterized by progressive and generalized degenerative loss of skeletal muscle mass, quality, and strength occurring during normal aging. Sarcopenia patients are mainly suffering from the loss in muscle strength and are faced with mobility disorders reducing their quality of life and are, therefore, at higher risk for morbidity (falls, bone fracture, metabolic diseases) and mortality.
Several molecular mechanisms have been described as causes for sarcopenia that refer to very different levels of muscle physiology. These mechanisms cover e. g. function of hormones (e. g. IGF-1 and Insulin), muscle fiber composition and neuromuscular drive, myo-satellite cell potential to differentiate and proliferate, inflammatory pathways as well as intracellular mechanisms in the processes of proteostasis and mitochondrial function.
In this review, we describe sarcopenia as a muscle-wasting syndrome distinct from other atrophic diseases and summarize the current view on molecular causes of sarcopenia development as well as open questions provoking further research efforts for establishing efficient lifestyle and therapeutic interventions.
KW - molecular pathways
KW - proteostasis
KW - proteasome
KW - autophagy
KW - mitochondria,
KW - muscle fibre composition
Y1 - 2020
U6 - https://doi.org/10.1016/j.arr.2020.101200
SN - 1568-1637
SN - 1872-9649
VL - 65
PB - Elsevier
CY - Clare
ER -