@article{MantzoukiLurlingFastneretal.2018,
author = {Mantzouki, Evanthia and Lurling, Miquel and Fastner, Jutta and Domis, Lisette Nicole de Senerpont and Wilk-Wozniak, Elzbieta and Koreiviene, Judita and Seelen, Laura and Teurlincx, Sven and Verstijnen, Yvon and Krzton, Wojciech and Walusiak, Edward and Karosiene, Jurate and Kasperoviciene, Jurate and Savadova, Ksenija and Vitonyte, Irma and Cillero-Castro, Carmen and Budzynska, Agnieszka and Goldyn, Ryszard and Kozak, Anna and Rosinska, Joanna and Szelag-Wasielewska, Elzbieta and Domek, Piotr and Jakubowska-Krepska, Natalia and Kwasizur, Kinga and Messyasz, Beata and Pelechata, Aleksandra and Pelechaty, Mariusz and Kokocinski, Mikolaj and Garcia-Murcia, Ana and Real, Monserrat and Romans, Elvira and Noguero-Ribes, Jordi and Parreno Duque, David and Fernandez-Moran, Elisabeth and Karakaya, Nusret and Haggqvist, Kerstin and Demir, Nilsun and Beklioglu, Meryem and Filiz, Nur and Levi, Eti E. and Iskin, Ugur and Bezirci, Gizem and Tavsanoglu, Ulku Nihan and Ozhan, Koray and Gkelis, Spyros and Panou, Manthos and Fakioglu, Ozden and Avagianos, Christos and Kaloudis, Triantafyllos and Celik, Kemal and Yilmaz, Mete and Marce, Rafael and Catalan, Nuria and Bravo, Andrea G. and Buck, Moritz and Colom-Montero, William and Mustonen, Kristiina and Pierson, Don and Yang, Yang and Raposeiro, Pedro M. and Goncalves, Vitor and Antoniou, Maria G. and Tsiarta, Nikoletta and McCarthy, Valerie and Perello, Victor C. and Feldmann, Tonu and Laas, Alo and Panksep, Kristel and Tuvikene, Lea and Gagala, Ilona and Mankiewicz-Boczek, Joana and Yagci, Meral Apaydin and Cinar, Sakir and Capkin, Kadir and Yagci, Abdulkadir and Cesur, Mehmet and Bilgin, Fuat and Bulut, Cafer and Uysal, Rahmi and Obertegger, Ulrike and Boscaini, Adriano and Flaim, Giovanna and Salmaso, Nico and Cerasino, Leonardo and Richardson, Jessica and Visser, Petra M. and Verspagen, Jolanda M. H. and Karan, Tunay and Soylu, Elif Neyran and Maraslioglu, Faruk and Napiorkowska-Krzebietke, Agnieszka and Ochocka, Agnieszka and Pasztaleniec, Agnieszka and Antao-Geraldes, Ana M. and Vasconcelos, Vitor and Morais, Joao and Vale, Micaela and Koker, Latife and Akcaalan, Reyhan and Albay, Meric and Maronic, Dubravka Spoljaric and Stevic, Filip and Pfeiffer, Tanja Zuna and Fonvielle, Jeremy Andre and Straile, Dietmar and Rothhaupt, Karl-Otto and Hansson, Lars-Anders and Urrutia-Cordero, Pablo and Blaha, Ludek and Geris, Rodan and Frankova, Marketa and Kocer, Mehmet Ali Turan and Alp, Mehmet Tahir and Remec-Rekar, Spela and Elersek, Tina and Triantis, Theodoros and Zervou, Sevasti-Kiriaki and Hiskia, Anastasia and Haande, Sigrid and Skjelbred, Birger and Madrecka, Beata and Nemova, Hana and Drastichova, Iveta and Chomova, Lucia and Edwards, Christine and Sevindik, Tugba Ongun and Tunca, Hatice and OEnem, Burcin and Aleksovski, Boris and Krstic, Svetislav and Vucelic, Itana Bokan and Nawrocka, Lidia and Salmi, Pauliina and Machado-Vieira, Danielle and de Oliveira, Alinne Gurjao and Delgado-Martin, Jordi and Garcia, David and Cereijo, Jose Luis and Goma, Joan and Trapote, Mari Carmen and Vegas-Vilarrubia, Teresa and Obrador, Biel and Grabowska, Magdalena and Karpowicz, Maciej and Chmura, Damian and Ubeda, Barbara and Angel Galvez, Jose and Ozen, Arda and Christoffersen, Kirsten Seestern and Warming, Trine Perlt and Kobos, Justyna and Mazur-Marzec, Hanna and Perez-Martinez, Carmen and Ramos-Rodriguez, Eloisa and Arvola, Lauri and Alcaraz-Parraga, Pablo and Toporowska, Magdalena and Pawlik-Skowronska, Barbara and Niedzwiecki, Michal and Peczula, Wojciech and Leira, Manel and Hernandez, Armand and Moreno-Ostos, Enrique and Maria Blanco, Jose and Rodriguez, Valeriano and Juan Montes-Perez, Jorge and Palomino, Roberto L. and Rodriguez-Perez, Estela and Carballeira, Rafael and Camacho, Antonio and Picazo, Antonio and Rochera, Carlos and Santamans, Anna C. and Ferriol, Carmen and Romo, Susana and Miguel Soria, Juan and Dunalska, Julita and Sienska, Justyna and Szymanski, Daniel and Kruk, Marek and Kostrzewska-Szlakowska, Iwona and Jasser, Iwona and Zutinic, Petar and Udovic, Marija Gligora and Plenkovic-Moraj, Andelka and Frak, Magdalena and Bankowska-Sobczak, Agnieszka and Wasilewicz, Michal and Ozkan, Korhan and Maliaka, Valentini and Kangro, Kersti and Grossart, Hans-Peter and Paerl, Hans W. and Carey, Cayelan C. and Ibelings, Bas W.},
title = {Temperature effects explain continental scale distribution of cyanobacterial toxins},
series = {Toxins},
volume = {10},
journal = {Toxins},
number = {4},
publisher = {MDPI},
address = {Basel},
issn = {2072-6651},
doi = {10.3390/toxins10040156},
pages = {24},
year = {2018},
abstract = {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.},
language = {en}
}
@article{MantzoukiCampbellvanLoonetal.2018,
author = {Mantzouki, Evanthia and Campbell, James and van Loon, Emiel and Visser, Petra and Konstantinou, Iosif and Antoniou, Maria and Giuliani, Gregory and Machado-Vieira, Danielle and de Oliveira, Alinne Gurjao and Maronic, Dubravka Spoljaric and Stevic, Filip and Pfeiffer, Tanja Zuna and Vucelic, Itana Bokan and Zutinic, Petar and Udovic, Marija Gligora and Plenkovic-Moraj, Andelka and Tsiarta, Nikoletta and Blaha, Ludek and Geris, Rodan and Frankova, Marketa and Christoffersen, Kirsten Seestern and Warming, Trine Perlt and Feldmann, Tonu and Laas, Alo and Panksep, Kristel and Tuvikene, Lea and Kangro, Kersti and Haggqvist, Kerstin and Salmi, Pauliina and Arvola, Lauri and Fastner, Jutta and Straile, Dietmar and Rothhaupt, Karl-Otto and Fonvielle, Jeremy Andre and Grossart, Hans-Peter and Avagianos, Christos and Kaloudis, Triantafyllos and Triantis, Theodoros and Zervou, Sevasti-Kiriaki and Hiskia, Anastasia and Gkelis, Spyros and Panou, Manthos and McCarthy, Valerie and Perello, Victor C. and Obertegger, Ulrike and Boscaini, Adriano and Flaim, Giovanna and Salmaso, Nico and Cerasino, Leonardo and Koreiviene, Judita and Karosiene, Jurate and Kasperoviciene, Jurate and Savadova, Ksenija and Vitonyte, Irma and Haande, Sigrid and Skjelbred, Birger and Grabowska, Magdalena and Karpowicz, Maciej and Chmura, Damian and Nawrocka, Lidia and Kobos, Justyna and Mazur-Marzec, Hanna and Alcaraz-Parraga, Pablo and Wilk-Wozniak, Elzbieta and Krzton, Wojciech and Walusiak, Edward and Gagala, Ilona and Mankiewicz-Boczek, Joana and Toporowska, Magdalena and Pawlik-Skowronska, Barbara and Niedzwiecki, Michal and Peczula, Wojciech and Napiorkowska-Krzebietke, Agnieszka and Dunalska, Julita and Sienska, Justyna and Szymanski, Daniel and Kruk, Marek and Budzynska, Agnieszka and Goldyn, Ryszard and Kozak, Anna and Rosinska, Joanna and Szelag-Wasielewska, Elzbieta and Domek, Piotr and Jakubowska-Krepska, Natalia and Kwasizur, Kinga and Messyasz, Beata and Pelechata, Aleksandra and Pelechaty, Mariusz and Kokocinski, Mikolaj and Madrecka, Beata and Kostrzewska-Szlakowska, Iwona and Frak, Magdalena and Bankowska-Sobczak, Agnieszka and Wasilewicz, Michal and Ochocka, Agnieszka and Pasztaleniec, Agnieszka and Jasser, Iwona and Antao-Geraldes, Ana M. and Leira, Manel and Hernandez, Armand and Vasconcelos, Vitor and Morais, Joao and Vale, Micaela and Raposeiro, Pedro M. and Goncalves, Vitor and Aleksovski, Boris and Krstic, Svetislav and Nemova, Hana and Drastichova, Iveta and Chomova, Lucia and Remec-Rekar, Spela and Elersek, Tina and Delgado-Martin, Jordi and Garcia, David and Luis Cereijo, Jose and Goma, Joan and Carmen Trapote, Mari and Vegas-Vilarrubia, Teresa and Obrador, Biel and Garcia-Murcia, Ana and Real, Monserrat and Romans, Elvira and Noguero-Ribes, Jordi and Parreno Duque, David and Fernandez-Moran, Elisabeth and Ubeda, Barbara and Angel Galvez, Jose and Marce, Rafael and Catalan, Nuria and Perez-Martinez, Carmen and Ramos-Rodriguez, Eloisa and Cillero-Castro, Carmen and Moreno-Ostos, Enrique and Maria Blanco, Jose and Rodriguez, Valeriano and Juan Montes-Perez, Jorge and Palomino, Roberto L. and Rodriguez-Perez, Estela and Carballeira, Rafael and Camacho, Antonio and Picazo, Antonio and Rochera, Carlos and Santamans, Anna C. and Ferriol, Carmen and Romo, Susana and Soria, Juan Miguel and Hansson, Lars-Anders and Urrutia-Cordero, Pablo and Ozen, Arda and Bravo, Andrea G. and Buck, Moritz and Colom-Montero, William and Mustonen, Kristiina and Pierson, Don and Yang, Yang and Verspagen, Jolanda M. H. and Domis, Lisette N. de Senerpont and Seelen, Laura and Teurlincx, Sven and Verstijnen, Yvon and Lurling, Miquel and Maliaka, Valentini and Faassen, Elisabeth J. and Latour, Delphine and Carey, Cayelan C. and Paerl, Hans W. and Torokne, Andrea and Karan, Tunay and Demir, Nilsun and Beklioglu, Meryem and Filiz, Nur and Levi, Eti E. and Iskin, Ugur and Bezirci, Gizem and Tavsanoglu, Ulku Nihan and Celik, Kemal and Ozhan, Koray and Karakaya, Nusret and Kocer, Mehmet Ali Turan and Yilmaz, Mete and Maraslioglu, Faruk and Fakioglu, Ozden and Soylu, Elif Neyran and Yagci, Meral Apaydin and Cinar, Sakir and Capkin, Kadir and Yagci, Abdulkadir and Cesur, Mehmet and Bilgin, Fuat and Bulut, Cafer and Uysal, Rahmi and Koker, Latife and Akcaalan, Reyhan and Albay, Meric and Alp, Mehmet Tahir and Ozkan, Korhan and Sevindik, Tugba Ongun and Tunca, Hatice and Onem, Burcin and Richardson, Jessica and Edwards, Christine and Bergkemper, Victoria and Beirne, Eilish and Cromie, Hannah and Ibelings, Bastiaan W.},
title = {Data Descriptor: A European Multi Lake Survey dataset of environmental variables, phytoplankton pigments and cyanotoxins},
series = {Scientific Data},
volume = {5},
journal = {Scientific Data},
publisher = {Nature Publ. Group},
address = {London},
issn = {2052-4463},
doi = {10.1038/sdata.2018.226},
pages = {13},
year = {2018},
abstract = {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.},
language = {en}
}
@misc{MantzoukiLuerlingFastneretal.2018,
author = {Mantzouki, Evanthia and L{\"u}rling, Miquel and Fastner, Jutta and Domis, Lisette Nicole de Senerpont and Wilk-Wo{\'{z}}niak, Elżbieta and Koreiviene, Judita and Seelen, Laura and Teurlincx, Sven and Verstijnen, Yvon and Krztoń, Wojciech and Walusiak, Edward and Karosienė, Jūratė and Kasperovičienė, Jūratė and Savadova, Ksenija and Vitonytė, Irma and Cillero-Castro, Carmen and Budzyńska, Agnieszka and Goldyn, Ryszard and Kozak, Anna and Rosińska, Joanna and Szeląg-Wasielewska, Elżbieta and Domek, Piotr and Jakubowska-Krepska, Natalia and Kwasizur, Kinga and Messyasz, Beata and Pełechata, Aleksandra and Pełechaty, Mariusz and Kokocinski, Mikolaj and Garc{\´i}a-Murcia, Ana and Real, Monserrat and Romans, Elvira and Noguero-Ribes, Jordi and Duque, David Parre{\~n}o and Fern{\´a}ndez-Mor{\´a}n, El{\´i}sabeth and Karakaya, Nusret and H{\"a}ggqvist, Kerstin and Beklioğlu, Meryem and Filiz, Nur and Levi, Eti E. and Iskin, Uğur and Bezirci, Gizem and Tav{\c{s}}anoğlu, {\"U}lk{\"u} Nihan and {\"O}zhan, Koray and Gkelis, Spyros and Panou, Manthos and Fakioglu, {\"O}zden and Avagianos, Christos and Kaloudis, Triantafyllos and {\c{C}}elik, Kemal and Yilmaz, Mete and Marc{\´e}, Rafael and Catal{\´a}n, Nuria and Bravo, Andrea G. and Buck, Moritz and Colom-Montero, William and Mustonen, Kristiina and Pierson, Don and Yang, Yang and Raposeiro, Pedro M. and Gon{\c{c}}alves, V{\´i}tor and Antoniou, Maria G. and Tsiarta, Nikoletta and McCarthy, Valerie and Perello, Victor C. and Feldmann, T{\~o}nu and Laas, Alo and Panksep, Kristel and Tuvikene, Lea and Gagala, Ilona and Mankiewicz-Boczek, Joana and Yağc{\i}, Meral Apayd{\i}n and {\c{C}}{\i}nar, Şakir and {\c{C}}apk{\i}n, Kadir and Yağc{\i}, Abdulkadir and Cesur, Mehmet and Bilgin, Fuat and Bulut, Cafer and Uysal, Rahmi and Obertegger, Ulrike and Boscaini, Adriano and Flaim, Giovanna and Salmaso, Nico and Cerasino, Leonardo and Richardson, Jessica and Visser, Petra M. and Verspagen, Jolanda M. H. and Karan, T{\"u}nay and Soylu, Elif Neyran and Mara{\c{s}}l{\i}oğlu, Faruk and Napi{\´o}rkowska-Krzebietke, Agnieszka and Ochocka, Agnieszka and Pasztaleniec, Agnieszka and Ant{\~a}o-Geraldes, Ana M. and Vasconcelos, Vitor and Morais, Jo{\~a}o and Vale, Micaela and K{\"o}ker, Latife and Ak{\c{c}}aalan, Reyhan and Albay, Meri{\c{c}} and Maronić, Dubravka Špoljarić and Stević, Filip and Pfeiffer, Tanja Žuna and Fonvielle, Jeremy Andre and Straile, Dietmar and Rothhaupt, Karl-Otto and Hansson, Lars-Anders and Urrutia-Cordero, Pablo and Bl{\´a}ha, Luděk and Geriš, Rodan and Fr{\´a}nkov{\´a}, Mark{\´e}ta and Ko{\c{c}}er, Mehmet Ali Turan and Alp, Mehmet Tahir and Remec-Rekar, Spela and Elersek, Tina and Triantis, Theodoros and Zervou, Sevasti-Kiriaki and Hiskia, Anastasia and Haande, Sigrid and Skjelbred, Birger and Madrecka, Beata and Nemova, Hana and Drastichova, Iveta and Chomova, Lucia and Edwards, Christine and Sevindik, Tuğba Ongun and Tunca, Hatice and {\"O}nem, Bur{\c{c}}in and Aleksovski, Boris and Krstić, Svetislav and Vucelić, Itana Bokan and Nawrocka, Lidia and Salmi, Pauliina and Machado-Vieira, Danielle and Oliveira, Alinne Gurj{\~a}o De and Delgado-Mart{\´i}n, Jordi and Garc{\´i}a, David and Cereijo, Jose Lu{\´i}s and Gom{\`a}, Joan and Trapote, Mari Carmen and Vegas-Vilarr{\´u}bia, Teresa and Obrador, Biel and Grabowska, Magdalena and Karpowicz, Maciej and Chmura, Damian and {\´U}beda, B{\´a}rbara and G{\´a}lvez, Jos{\´e} {\´A}ngel and {\"O}zen, Arda and Christoffersen, Kirsten Seestern and Warming, Trine Perlt and Kobos, Justyna and Mazur-Marzec, Hanna and P{\´e}rez-Mart{\´i}nez, Carmen and Ramos-Rodr{\´i}guez, Elo{\´i}sa and Arvola, Lauri and Alcaraz-P{\´a}rraga, Pablo and Toporowska, Magdalena and Pawlik-Skowronska, Barbara and Nied{\'{z}}wiecki, Michał and Pęczuła, Wojciech and Leira, Manel and Hern{\´a}ndez, Armand and Moreno-Ostos, Enrique and Blanco, Jos{\´e} Mar{\´i}a and Rodr{\´i}guez, Valeriano and Montes-P{\´e}rez, Jorge Juan and Palomino, Roberto L. and Rodr{\´i}guez-P{\´e}rez, Estela and Carballeira, Rafael and Camacho, Antonio and Picazo, Antonio and Rochera, Carlos and Santamans, Anna C. and Ferriol, Carmen and Romo, Susana and Soria, Juan Miguel and Dunalska, Julita and Sieńska, Justyna and Szymański, Daniel and Kruk, Marek and Kostrzewska-Szlakowska, Iwona and Jasser, Iwona and Žutinić, Petar and Udovič, Marija Gligora and Plenković-Moraj, Anđelka and Frąk, Magdalena and Bańkowska-Sobczak, Agnieszka and Wasilewicz, Michał and {\"O}zkan, Korhan and Maliaka, Valentini and Kangro, Kersti and Grossart, Hans-Peter and Paerl, Hans W. and Carey, Cayelan C. and Ibelings, Bas W.},
title = {Temperature effects explain continental scale distribution of cyanobacterial toxins},
series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
number = {1105},
issn = {1866-8372},
doi = {10.25932/publishup-42790},
url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-427902},
pages = {26},
year = {2018},
abstract = {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.},
language = {en}
}
@article{HenkelColemanSchraplauetal.2017,
author = {Henkel, Janin and Coleman, Charles Dominic and Schraplau, Anne and J{\"o}hrens, Korinna and Weber, Daniela and Castro, Jose Pedro and Hugo, Martin and Schulz, Tim Julius and Kr{\"a}mer, Stephanie and Sch{\"u}rmann, Annette and P{\"u}schel, Gerhard Paul},
title = {Induction of Steatohepatitis (NASH) with Insulin Resistance in Wild-type B6 Mice by a Western-type Diet Containing Soybean Oil and Cholesterol},
series = {Molecular medicine},
volume = {23},
journal = {Molecular medicine},
publisher = {Feinstein Inst. for Medical Research},
address = {Manhasset},
issn = {1076-1551},
doi = {10.2119/molmed.2016.00203},
pages = {70 -- 82},
year = {2017},
abstract = {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.},
language = {en}
}
@misc{HenkelBuchheimDieckowCastroetal.2019,
author = {Henkel, Janin and Buchheim-Dieckow, Katja and Castro, Jos{\´e} Pedro and Laeger, Thomas and Wardelmann, Kristina and Kleinridders, Andr{\´e} and J{\"o}hrens, Korinna and P{\"u}schel, Gerhard Paul},
title = {Reduced Oxidative Stress and Enhanced FGF21 Formation in Livers of Endurance-Exercised Rats with Diet-Induced NASH},
series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
number = {807},
issn = {1866-8372},
doi = {10.25932/publishup-44238},
url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-442384},
pages = {17},
year = {2019},
abstract = {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.},
language = {en}
}
@article{HenkelBuchheimDieckowCastroetal.2019,
author = {Henkel, Janin and Buchheim-Dieckow, Katja and Castro, Jos{\´e} Pedro and Laeger, Thomas and Wardelmann, Kristina and Kleinridders, Andr{\´e} and J{\"o}hrens, Korinna and P{\"u}schel, Gerhard Paul},
title = {Reduced Oxidative Stress and Enhanced FGF21 Formation in Livers of Endurance-Exercised Rats with Diet-Induced NASH},
series = {Nutrients},
volume = {11},
journal = {Nutrients},
number = {11},
publisher = {MDPI},
address = {Basel},
issn = {2072-6643},
doi = {10.3390/nu11112709},
pages = {15},
year = {2019},
abstract = {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.},
language = {en}
}
@article{HenkelAlfineSainetal.2018,
author = {Henkel, Janin and Alfine, Eugenia and Sa{\´i}n, Juliana and J{\"o}hrens, Korinna and Weber, Daniela and Castro, Jos{\´e} Pedro and K{\"o}nig, Jeannette and Stuhlmann, Christin and Vahrenbrink, Madita and Jonas, Wenke and Kleinridders, Andr{\´e} and P{\"u}schel, Gerhard Paul},
title = {Soybean Oil-Derived Poly-Unsaturated Fatty Acids Enhance Liver Damage in NAFLD Induced by Dietary Cholesterol},
series = {Nutrients},
volume = {10},
journal = {Nutrients},
number = {9},
publisher = {Molecular Diversity Preservation International (MDPI)},
address = {Basel},
issn = {2072-6643},
doi = {10.3390/nu10091326},
pages = {1 -- 17},
year = {2018},
abstract = {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.},
language = {en}
}
@misc{HenkelAlfineSainetal.2018,
author = {Henkel, Janin and Alfine, Eugenia and Sa{\´i}n, Juliana and J{\"o}hrens, Korinna and Weber, Daniela and Castro, Jos{\´e} Pedro and K{\"o}nig, Jeannette and Stuhlmann, Christin and Vahrenbrink, Madita and Jonas, Wenke and Kleinridders, Andr{\´e} and P{\"u}schel, Gerhard Paul},
title = {Soybean Oil-Derived Poly-Unsaturated Fatty Acids Enhance Liver Damage in NAFLD Induced by Dietary Cholesterol},
series = {Nutrients},
journal = {Nutrients},
url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-419773},
pages = {17},
year = {2018},
abstract = {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.},
language = {en}
}
@article{CastroFernandoReegetal.2019,
author = {Castro, Jose Pedro and Fernando, Raquel and Reeg, Sandra and Meinl, Walter and Almeida, Henrique and Grune, Tilman},
title = {Non-enzymatic cleavage of Hsp90 by oxidative stress leads to actin aggregate formation},
series = {Redox Biology},
volume = {21},
journal = {Redox Biology},
publisher = {Elsevier},
address = {Amsterdam},
issn = {2213-2317},
doi = {10.1016/j.redox.2019.101108},
pages = {10},
year = {2019},
abstract = {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.},
language = {en}
}
@article{WiedmerJungCastroetal.2020,
author = {Wiedmer, Petra and Jung, Tobias and Castro, Jose Pedro and Pomatto, Laura C. D. and Sun, Patrick Y. and Davies, Kelvin J. A. and Grune, Tilman},
title = {Sarcopenia},
series = {Ageing research reviews : ARR},
volume = {65},
journal = {Ageing research reviews : ARR},
publisher = {Elsevier},
address = {Clare},
issn = {1568-1637},
doi = {10.1016/j.arr.2020.101200},
pages = {17},
year = {2020},
abstract = {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.},
language = {en}
}
@misc{CastroGruneSpeckmann2016,
author = {Castro, Jos{\´e} Pedro and Grune, Tilman and Speckmann, Bodo},
title = {The two faces of reactive oxygen species (ROS) in adipocyte function and dysfunction},
series = {Biological chemistry},
volume = {397},
journal = {Biological chemistry},
publisher = {De Gruyter},
address = {Berlin},
issn = {1431-6730},
doi = {10.1515/hsz-2015-0305},
pages = {709 -- 724},
year = {2016},
abstract = {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.},
language = {en}
}
@article{CastroWardelmannGruneetal.2018,
author = {Castro, Jose Pedro and Wardelmann, Kristina and Grune, Tilman and Kleinridders, Andre},
title = {Mitochondrial Chaperones in the Brain},
series = {Frontiers in Endocrinology},
volume = {9},
journal = {Frontiers in Endocrinology},
publisher = {Frontiers Research Foundation},
address = {Lausanne},
issn = {1664-2392},
doi = {10.3389/fendo.2018.00196},
pages = {13},
year = {2018},
abstract = {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.},
language = {en}
}
@article{ReegJungCastroetal.2016,
author = {Reeg, Sandra and Jung, Tobias and Castro, Jos{\´e} Pedro and Davies, Kelvin J. A. and Henze, Andrea and Grune, Tilman},
title = {The molecular chaperone Hsp70 promotes the proteolytic removal of oxidatively damaged proteins by the proteasome},
series = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
volume = {99},
journal = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
publisher = {Elsevier},
address = {New York},
issn = {0891-5849},
doi = {10.1016/j.freeradbiomed.2016.08.002},
pages = {153 -- 166},
year = {2016},
abstract = {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/).},
language = {en}
}
@article{NowotnyCastroHugoetal.2018,
author = {Nowotny, Kerstin and Castro, Jose Pedro and Hugo, Martin and Braune, Sabine and Weber, Daniela and Pignitter, Marc and Somoza, Veronika and Bornhorst, Julia and Schwerdtle, Tanja and Grune, Tilman},
title = {Oxidants produced by methylglyoxal-modified collagen trigger ER stress and apoptosis in skin fibroblasts},
series = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
volume = {120},
journal = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
publisher = {Elsevier},
address = {New York},
issn = {0891-5849},
doi = {10.1016/j.freeradbiomed.2018.03.022},
pages = {102 -- 113},
year = {2018},
abstract = {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.},
language = {en}
}
@article{FernandoDrescherNowotnyetal.2018,
author = {Fernando, Raquel and Drescher, Cathleen and Nowotny, Kerstin and Grune, Tilman and Castro, Jose Pedro},
title = {Impaired proteostasis during skeletal muscle aging},
series = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
volume = {132},
journal = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
publisher = {Elsevier},
address = {New York},
issn = {0891-5849},
doi = {10.1016/j.freeradbiomed.2018.08.037},
pages = {58 -- 66},
year = {2018},
abstract = {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.},
language = {en}
}
@misc{CastroWardelmannGruneetal.2018,
author = {Castro, Jos{\´e} Pedro and Wardelmann, Kristina and Grune, Tilman and Kleinridders, Andr{\´e}},
title = {Mitochondrial chaperones in the brain},
series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
number = {1031},
issn = {1866-8372},
doi = {10.25932/publishup-46065},
url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-460650},
pages = {15},
year = {2018},
abstract = {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.},
language = {en}
}
@misc{FernandoDrescherDeubeletal.2018,
author = {Fernando, Raquel and Drescher, Cathleen and Deubel, Stefanie and Grune, Tilman and Castro, Jose Pedro},
title = {Distinct proteasomal activity for fast and slow twitch skeletal muscle during aging},
series = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
volume = {120},
journal = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
publisher = {Elsevier},
address = {New York},
issn = {0891-5849},
doi = {10.1016/j.freeradbiomed.2018.04.393},
pages = {S119 -- S119},
year = {2018},
abstract = {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.},
language = {en}
}
@misc{CastroGruneSpeckmann2017,
author = {Castro, Jos{\´e} Pedro and Grune, Tilman and Speckmann, Bodo},
title = {The two faces of reactive oxygen species (ROS) in adipocyte function and dysfunction},
url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-398039},
pages = {16},
year = {2017},
abstract = {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.},
language = {en}
}
@article{FernandoDrescherDeubeletal.2018,
author = {Fernando, Raquel and Drescher, Cathleen and Deubel, Stefanie and Jung, Tobias and Ost, Mario and Klaus, Susanne and Grune, Tilman and Castro, Jose Pedro},
title = {Low proteasomal activity in fast skeletal muscle fibers is not associated with increased age-related oxidative damage},
series = {Experimental gerontology},
volume = {117},
journal = {Experimental gerontology},
publisher = {Elsevier},
address = {Oxford},
issn = {0531-5565},
doi = {10.1016/j.exger.2018.10.018},
pages = {45 -- 52},
year = {2018},
abstract = {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.},
language = {en}
}
@misc{WardelmannRathCastroetal.2021,
author = {Wardelmann, Kristina and Rath, Michaela and Castro, Jos{\´e} Pedro and Bl{\"u}mel, Sabine and Schell, Mareike and Hauffe, Robert and Schumacher, Fabian and Flore, Tanina and Ritter, Katrin and Wernitz, Andreas and Hosoi, Toru and Ozawa, Koichiro and Kleuser, Burkhard and Weiß, J{\"u}rgen and Sch{\"u}rmann, Annette and Kleinridders, Andr{\´e}},
title = {Central acting Hsp10 regulates mitochondrial function, fatty acid metabolism and insulin sensitivity in the hypothalamus},
series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
number = {5},
issn = {1866-8372},
doi = {10.25932/publishup-52298},
url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-522985},
pages = {24},
year = {2021},
abstract = {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.},
language = {en}
}
@article{WardelmannRathCastroetal.2021,
author = {Wardelmann, Kristina and Rath, Michaela and Castro, Jos{\´e} Pedro and Bl{\"u}mel, Sabine and Schell, Mareike and Hauffe, Robert and Schumacher, Fabian and Flore, Tanina and Ritter, Katrin and Wernitz, Andreas and Hosoi, Toru and Ozawa, Koichiro and Kleuser, Burkhard and Weiß, J{\"u}rgen and Sch{\"u}rmann, Annette and Kleinridders, Andr{\´e}},
title = {Central acting Hsp10 regulates mitochondrial function, fatty acid metabolism and insulin sensitivity in the hypothalamus},
series = {Antioxidants},
volume = {10},
journal = {Antioxidants},
number = {5},
publisher = {MDPI},
address = {Basel},
issn = {2076-3921},
doi = {10.3390/antiox10050711},
pages = {22},
year = {2021},
abstract = {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.},
language = {en}
}