@misc{HauffeRathSchelletal.2022,
  author    = {Hauffe, Robert and Rath, Michaela and Schell, Mareike and Ritter, Katrin and Kappert, Kai and Deubel, Stefanie and Ott, Christiane and J{\"a}hnert, Markus and Jonas, Wenke and Sch{\"u}rmann, Annette and Kleinridders, Andr{\´e}},
  title     = {HSP60 reduction protects against diet-induced obesity by modulating energy metabolism in adipose tissue},
  series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  publisher = {Universit{\"a}tsverlag Potsdam},
  address   = {Potsdam},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-54800},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-548002},
  pages     = {1 -- 14},
  year      = {2022},
  abstract  = {Objective Insulin regulates mitochondrial function, thereby propagating an efficient metabolism. Conversely, diabetes and insulin resistance are linked to mitochondrial dysfunction with a decreased expression of the mitochondrial chaperone HSP60. The aim of this investigation was to determine the effect of a reduced HSP60 expression on the development of obesity and insulin resistance. Methods Control and heterozygous whole-body HSP60 knockout (Hsp60+/-) mice were fed a high-fat diet (HFD, 60\% calories from fat) for 16 weeks and subjected to extensive metabolic phenotyping. To understand the effect of HSP60 on white adipose tissue, microarray analysis of gonadal WAT was performed, ex vivo experiments were performed, and a lentiviral knockdown of HSP60 in 3T3-L1 cells was conducted to gain detailed insights into the effect of reduced HSP60 levels on adipocyte homeostasis. Results Male Hsp60+/- mice exhibited lower body weight with lower fat mass. These mice exhibited improved insulin sensitivity compared to control, as assessed by Matsuda Index and HOMA-IR. Accordingly, insulin levels were significantly reduced in Hsp60+/- mice in a glucose tolerance test. However, Hsp60+/- mice exhibited an altered adipose tissue metabolism with elevated insulin-independent glucose uptake, adipocyte hyperplasia in the presence of mitochondrial dysfunction, altered autophagy, and local insulin resistance. Conclusions We discovered that the reduction of HSP60 in mice predominantly affects adipose tissue homeostasis, leading to beneficial alterations in body weight, body composition, and adipocyte morphology, albeit exhibiting local insulin resistance.},
  language  = {en}
}
@article{HauffeRathSchelletal.2021,
  author    = {Hauffe, Robert and Rath, Michaela and Schell, Mareike and Ritter, Katrin and Kappert, Kai and Deubel, Stefanie and Ott, Christiane and J{\"a}hnert, Markus and Jonas, Wenke and Sch{\"u}rmann, Annette and Kleinridders, Andr{\´e}},
  title     = {HSP60 reduction protects against diet-induced obesity by modulating energy metabolism in adipose tissue},
  series = {Molecular Metabolism},
  volume    = {53},
  journal   = {Molecular Metabolism},
  publisher = {Elsevier},
  address   = {Amsterdam, Niederlande},
  issn      = {2212-8778},
  doi       = {10.1016/j.molmet.2021.101276},
  pages     = {1 -- 14},
  year      = {2021},
  abstract  = {Objective Insulin regulates mitochondrial function, thereby propagating an efficient metabolism. Conversely, diabetes and insulin resistance are linked to mitochondrial dysfunction with a decreased expression of the mitochondrial chaperone HSP60. The aim of this investigation was to determine the effect of a reduced HSP60 expression on the development of obesity and insulin resistance. Methods Control and heterozygous whole-body HSP60 knockout (Hsp60+/-) mice were fed a high-fat diet (HFD, 60\% calories from fat) for 16 weeks and subjected to extensive metabolic phenotyping. To understand the effect of HSP60 on white adipose tissue, microarray analysis of gonadal WAT was performed, ex vivo experiments were performed, and a lentiviral knockdown of HSP60 in 3T3-L1 cells was conducted to gain detailed insights into the effect of reduced HSP60 levels on adipocyte homeostasis. Results Male Hsp60+/- mice exhibited lower body weight with lower fat mass. These mice exhibited improved insulin sensitivity compared to control, as assessed by Matsuda Index and HOMA-IR. Accordingly, insulin levels were significantly reduced in Hsp60+/- mice in a glucose tolerance test. However, Hsp60+/- mice exhibited an altered adipose tissue metabolism with elevated insulin-independent glucose uptake, adipocyte hyperplasia in the presence of mitochondrial dysfunction, altered autophagy, and local insulin resistance. Conclusions We discovered that the reduction of HSP60 in mice predominantly affects adipose tissue homeostasis, leading to beneficial alterations in body weight, body composition, and adipocyte morphology, albeit exhibiting local insulin resistance.},
  language  = {en}
}
@misc{AichertStaigerSchulteMaeteretal.2010,
  author    = {Aichert, Ingrid and Staiger, Anja and Schulte-M{\"a}ter, Anne and Becker-Redding, Ulrike and Stahn, Corinna and Peschke, Claudia and Heide, Judith and Ott, Susan and Herrmann, Heike and V{\"o}lsch, Juliane and Mayer, J{\"o}rg and Rohnke, Lucie and Frank, Ulrike and Stadie, Nicole and Jentsch, Nadine and Blech, Anke and Kurtenbach, Stephanie and Thieke, Johanna and Schr{\"o}der, Astrid and Stahn, Corinna and H{\"o}rnig, Robin and Burchert, Frank and De Bleser, Ria and Heister, Julian and Bartels, Luise and W{\"u}rzner, Kay-Michael and B{\"o}hme, Romy and Burmester, Juliane and Krajewski, Melanie and Nager, Wido and Jungeh{\"u}lsing, Gerhard Jan and Wartenburger, Isabell and J{\"o}bges, Michael and Schwilling, Eleonore and Lidzba, Karen and Winkler, Susanne and Konietzko, Andreas and Kr{\"a}geloh-Mann, Ingeborg and Rilling, Eva and Wilken, Rainer and Wismann, Kathrin and Glandorf, Birte and Hoffmann, Hannah and Hinnenkamp, Christiane and Rohlmann, Insa and Ludewigt, Jacqueline and Bittner, Christian and Orlov, Tatjana and Claus, Katrin and Ehemann, Christine and Winnecken, Andreas and Hummel, Katja and Breitenstein, Sarah},
  title     = {Spektrum Patholinguistik = Schwerpunktthema: Von der Programmierung zur Artikulation : Sprechapraxie bei Kindern und Erwachsenen},
  number    = {3},
  editor    = {Wahl, Michael and Stahn, Corinna and Hanne, Sandra and Fritzsche, Tom},
  publisher = {Universit{\"a}tsverlag Potsdam},
  address   = {Potsdam},
  organization    = {Verband f{\"u}r Patholinguistik e. V. (vpl)},
  isbn      = {978-3-86956-079-3},
  issn      = {1869-3822},
  doi       = {10.25932/publishup-4578},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-45470},
  year      = {2010},
  abstract  = {Das 3. Herbsttreffen Patholinguistik fand am 21. November 2009 an der Universit{\"a}t Potsdam statt. Der vorliegende Tagungsband enth{\"a}lt die drei Hauptvortr{\"a}ge zum Schwerpunktthema „Von der Programmierung zu Artikulation: Sprechapraxie bei Kindern und Erwachsenen". Dar{\"u}ber hinaus enth{\"a}lt der Band die Beitr{\"a}ge aus dem Spektrum Patholinguistik, sowie die Abstracts der Posterpr{\"a}sentationen.},
  language  = {de}
}
@phdthesis{Ott2016,
  author    = {Ott, Christiane},
  title     = {Untersuchung der intrazellul{\"a}ren Proteolyse w{\"a}hrend der Zellalterung},
  school      = {Universit{\"a}t Potsdam},
  pages     = {100},
  year      = {2016},
  language  = {de}
}
@article{HoffmannOttRaupbachetal.2022,
  author    = {Hoffmann, Holger and Ott, Christiane and Raupbach, Jana and Andernach, Lars and Renz, Matthias and Grune, Tilman and Hanschen, Franziska S.},
  title     = {Assessing bioavailability and bioactivity of 4-Hydroxythiazolidine-2-Thiones, newly discovered glucosinolate degradation products formed during domestic boiling of cabbage},
  series = {Frontiers in nutrition},
  volume    = {9},
  journal   = {Frontiers in nutrition},
  publisher = {Frontiers Media},
  address   = {Lausanne},
  issn      = {2296-861X},
  doi       = {10.3389/fnut.2022.941286},
  pages     = {13},
  year      = {2022},
  abstract  = {Glucosinolates are plant secondary metabolites found in cruciferous vegetables (Brassicaceae) that are valued for their potential health benefits. Frequently consumed representatives of these vegetables, for example, are white or red cabbage, which are typically boiled before consumption. Recently, 3-alk(en)yl-4-hydroxythiazolidine-2-thiones were identified as a class of thermal glucosinolate degradation products that are formed during the boiling of cabbage. Since these newly discovered compounds are frequently consumed, this raises questions about their potential uptake and their possible bioactive functions. Therefore, 3-allyl-4-hydroxythiazolidine-2-thione (allyl HTT) and 4-hydroxy-3-(4-(methylsulfinyl) butyl)thiazolidine-2-thione (4-MSOB HTT) as degradation products of the respective glucosinolates sinigrin and glucoraphanin were investigated. After consumption of boiled red cabbage broth, recoveries of consumed amounts of the degradation products in urine collected for 24 h were 18 +/- 5\% for allyl HTT and 21 +/- 4\% for 4-MSOB HTT (mean +/- SD, n = 3). To investigate the stability of the degradation products during uptake and to elucidate the uptake mechanism, both an in vitro stomach and an in vitro intestinal model were applied. The results indicate that the uptake of allyl HTT and 4-MSOB HTT occurs by passive diffusion. Both compounds show no acute cell toxicity, no antioxidant potential, and no change in NAD(P)H dehydrogenase quinone 1 (NQO1) activity up to 100 mu M. However, inhibition of glycogen synthase kinases-3 (GSK-3) in the range of 20\% for allyl HTT for the isoform GSK-3 beta and 29\% for 4-MSOB HTT for the isoform GSK-3 alpha at a concentration of 100 mu M was found. Neither health-promoting nor toxic effects of 3-alk(en)yl-4-hydroxythiazolidine-2-thiones were found in the four tested assays carried out in this study, which contrasts with the properties of other glucosinolate degradation products, such as isothiocyanates.},
  language  = {en}
}
@article{JohnGruneOttetal.2018,
  author    = {John, Cathleen and Grune, Jana and Ott, Christiane and Nowotny, Kerstin and Deubel, Stefanie and K{\"u}hne, Arne and Schubert, Carola and Kintscher, Ulrich and Regitz-Zagrosek, Vera and Grune, Tilman},
  title     = {Sex Differences in Cardiac Mitochondria in the New Zealand Obese Mouse},
  series = {Frontiers in Endocrinology},
  volume    = {9},
  journal   = {Frontiers in Endocrinology},
  publisher = {Frontiers Research Foundation},
  address   = {Lausanne},
  issn      = {1664-2392},
  doi       = {10.3389/fendo.2018.00732},
  pages     = {9},
  year      = {2018},
  abstract  = {Background: Obesity is a risk factor for diseases including type 2 diabetes mellitus (T2DM) and cardiovascular disorders. Diabetes itself contributes to cardiac damage. Thus, studying cardiovascular events and establishing therapeutic intervention in the period of type T2DM onset and manifestation are of highest importance. Mitochondrial dysfunction is one of the pathophysiological mechanisms leading to impaired cardiac function. Methods: An adequate animal model for studying pathophysiology of T2DM is the New Zealand Obese (NZO) mouse. These mice were maintained on a high-fat diet (HFD) without carbohydrates for 13 weeks followed by 4 week HFD with carbohydrates. NZO mice developed severe obesity and only male mice developed manifest T2DM. We determined cardiac phenotypes and mitochondrial function as well as cardiomyocyte signaling in this model. Results: The development of an obese phenotype and T2DM in male mice was accompanied by an impaired systolic function as judged by echocardiography and MyH6/7 expression. Moreover, the mitochondrial function only in male NZO hearts was significantly reduced and ERK1/2 and AMPK protein levels were altered. Conclusions: This is the first report demonstrating that the cardiac phenotype in male diabetic NZO mice is associated with impaired cardiac energy function and signaling events.},
  language  = {en}
}
@misc{KoenigGruneOtt2019,
  author    = {K{\"o}nig, Jeannette and Grune, Tilman and Ott, Christiane},
  title     = {Assessing autophagy in murine skeletal muscle: current findings to modulate and quantify the autophagic flux},
  series = {Current opinion in clinical nutrition and metabolic care},
  volume    = {22},
  journal   = {Current opinion in clinical nutrition and metabolic care},
  number    = {5},
  publisher = {Lippincott Williams \& Wilkins},
  address   = {Philadelphia},
  issn      = {1363-1950},
  doi       = {10.1097/MCO.0000000000000579},
  pages     = {355 -- 362},
  year      = {2019},
  abstract  = {Purpose of review In addition to the currently available lysosomotropic drugs and autophagy whole-body knockout mouse models, we provide alternative methods that enable the modulation and detection of autophagic flux in vivo, discussing advantages and disadvantages of each method. Recent findings With the autophagosome-lysosome fusion inhibitor colchicine in skeletal muscle and temporal downregulation of autophagy using a novel Autophagy related 5-short hairpin RNA (Atg5-shRNA) mouse model we mention two models that directly modulate autophagy flux in vivo. Furthermore, methods to quantify autophagy flux, such as mitophagy transgenic reporters, in situ immunofluorescent staining and multispectral imaging flow cytometry, in mature skeletal muscle and cells are addressed. To achieve clinical benefit, less toxic, temporary and cell-type-specific modulation of autophagy should be pursued further. A temporary knockdown as described for the Atg5-shRNA mice could provide a first insight into possible implications of autophagy inhibition. However, it is also important to take a closer look into the methods to evaluate autophagy after harvesting the tissue. In particular caution is required when experimental conditions can influence the final measurement and this should be pretested carefully.},
  language  = {en}
}
@article{SchroeterNeugartSchreineretal.2019,
  author    = {Schr{\"o}ter, David and Neugart, Susanne and Schreiner, Monika and Grune, Tilman and Rohn, Sascha and Ott, Christiane},
  title     = {Amaranth's 2-Caffeoylisocitric Acid—An Anti-Inflammatory Caffeic Acid Derivative That Impairs NF-κB Signaling in LPS-Challenged RAW 264.7 Macrophages},
  series = {Nutrients},
  volume    = {11},
  journal   = {Nutrients},
  number    = {3},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2072-6643},
  doi       = {10.3390/nu11030571},
  pages     = {14},
  year      = {2019},
  abstract  = {For centuries, Amaranthus sp. were used as food, ornamentals, and medication. Molecular mechanisms, explaining the health beneficial properties of amaranth, are not yet understood, but have been attributed to secondary metabolites, such as phenolic compounds. One of the most abundant phenolic compounds in amaranth leaves is 2-caffeoylisocitric acid (C-IA) and regarding food occurrence, C-IA is exclusively found in various amaranth species. In the present study, the anti-inflammatory activity of C-IA, chlorogenic acid, and caffeic acid in LPS-challenged macrophages (RAW 264.7) has been investigated and cellular contents of the caffeic acid derivatives (CADs) were quantified in the cells and media. The CADs were quantified in the cell lysates in nanomolar concentrations, indicating a cellular uptake. Treatment of LPS-challenged RAW 264.7 cells with 10 µM of CADs counteracted the LPS effects and led to significantly lower mRNA and protein levels of inducible nitric oxide synthase, tumor necrosis factor alpha, and interleukin 6, by directly decreasing the translocation of the nuclear factor κB/Rel-like containing protein 65 into the nucleus. This work provides new insights into the molecular mechanisms that attribute to amaranth's anti-inflammatory properties and highlights C-IA's potential as a health-beneficial compound for future research.},
  language  = {en}
}
@misc{RaupbachOttKoenigetal.2020,
  author    = {Raupbach, Jana and Ott, Christiane and K{\"o}nig, Jeannette and Grune, Tilman},
  title     = {Proteasomal degradation of glycated proteins depends on substrate unfolding},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-52757},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-527570},
  pages     = {516 -- 524},
  year      = {2020},
  abstract  = {The Maillard reaction generates protein modifications which can accumulate during hyperglycemia or aging and may have inflammatory consequences. The proteasome is one of the major intracellular systems involved in the proteolytic degradation of modified proteins but its role in the degradation of glycated proteins is scarcely studied. In this study, chemical and structural changes of glycated myoglobin were analyzed and its degradation by 20S proteasome was studied. Myoglobin was incubated with physiological (5-10 mM), moderate (50-100 mM) and severe levels (300 mM) of glucose or methylglyoxal (MGO, 50 mM). Glycation increased myoglobin's fluorescence and surface hydrophobicity. Severe glycation generated crosslinked proteins as shown by gel electrophoresis. The concentration of advanced glycation endproducts (AGEs) N-epsilon-carboxymethyl lysine (CML), N-epsilon-carboxyethyl lysine (CEL), methylglyoxal-derived hydroimidazolone-1 (MG-H1), pentosidine and pyrraline was analyzed after enzymatic hydrolysis followed by UPLC-MS/MS. Higher concentrations of glucose increased all analyzed AGEs and incubation with MGO led to a pronounced increase of CEL and MG-H1. The binding of the heme group to apo-myoglobin was decreased with increasing glycation indicating the loss of tertiary protein structure. Proteasomal degradation of modified myoglobin compared to native myoglobin depends on the degree of glycation: physiological conditions decreased proteasomal degradation whereas moderate glycation increased degradation. Severe glycation again decreased proteolytic cleavage which might be due to crosslinking of protein monomers. The activity of the proteasomal subunit beta 5 is influenced by the presence of glycated myoglobin. In conclusion, the role of the proteasome in the degradation of glycated proteins is highly dependent on the level of glycation and consequent protein unfolding.},
  language  = {en}
}
@article{HaeseliDeubelJungetal.2020,
  author    = {H{\"a}seli, Steffen and Deubel, Stefanie and Jung, Tobias and Grune, Tilman and Ott, Christiane},
  title     = {Cardiomyocyte contractility and autophagy in a premature senescence model of cardiac aging},
  series = {Oxidative medicine and cellular longevity},
  volume    = {2020},
  journal   = {Oxidative medicine and cellular longevity},
  number    = {Special Issue},
  publisher = {Landes Bioscience},
  address   = {Austin, Tex.},
  issn      = {1942-0994},
  doi       = {10.1155/2020/8141307},
  pages     = {14},
  year      = {2020},
  abstract  = {Globally, cardiovascular diseases are the leading cause of death in the aging population. While the clinical pathology of the aging heart is thoroughly characterized, underlying molecular mechanisms are still insufficiently clarified. The aim of the present study was to establish an in vitro model system of cardiomyocyte premature senescence, culturing heart muscle cells derived from neonatal C57Bl/6J mice for 21 days. Premature senescence of neonatal cardiac myocytes was induced by prolonged culture time in an oxygen-rich postnatal environment. Age-related changes in cellular function were determined by senescence-associated beta-galactosidase activity, increasing presence of cell cycle regulators, such as p16, p53, and p21, accumulation of protein aggregates, and restricted proteolysis in terms of decreasing (macro-)autophagy. Furthermore, the culture system was functionally characterized for alterations in cell morphology and contractility. An increase in cellular size associated with induced expression of atrial natriuretic peptides demonstrated a stress-induced hypertrophic phenotype in neonatal cardiomyocytes. Using the recently developed analytical software tool Myocyter, we were able to show a spatiotemporal constraint in spontaneous contraction behavior during cultivation. Within the present study, the 21-day culture of neonatal cardiomyocytes was defined as a functional model system of premature cardiac senescence to study age-related changes in cardiomyocyte contractility and autophagy.},
  language  = {en}
}
@article{RaupbachOttKoenigetal.2020,
  author    = {Raupbach, Jana and Ott, Christiane and K{\"o}nig, Jeannette and Grune, Tilman},
  title     = {Proteasomal degradation of glycated proteins depends on substrate unfolding: Preferred degradation of moderately modified myoglobin},
  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    = {152},
  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.2019.11.024},
  pages     = {516 -- 524},
  year      = {2020},
  abstract  = {The Maillard reaction generates protein modifications which can accumulate during hyperglycemia or aging and may have inflammatory consequences. The proteasome is one of the major intracellular systems involved in the proteolytic degradation of modified proteins but its role in the degradation of glycated proteins is scarcely studied. In this study, chemical and structural changes of glycated myoglobin were analyzed and its degradation by 20S proteasome was studied. Myoglobin was incubated with physiological (5-10 mM), moderate (50-100 mM) and severe levels (300 mM) of glucose or methylglyoxal (MGO, 50 mM). Glycation increased myoglobin's fluorescence and surface hydrophobicity. Severe glycation generated crosslinked proteins as shown by gel electrophoresis. The concentration of advanced glycation endproducts (AGEs) N-epsilon-carboxymethyl lysine (CML), N-epsilon-carboxyethyl lysine (CEL), methylglyoxal-derived hydroimidazolone-1 (MG-H1), pentosidine and pyrraline was analyzed after enzymatic hydrolysis followed by UPLC-MS/MS. Higher concentrations of glucose increased all analyzed AGEs and incubation with MGO led to a pronounced increase of CEL and MG-H1. The binding of the heme group to apo-myoglobin was decreased with increasing glycation indicating the loss of tertiary protein structure. Proteasomal degradation of modified myoglobin compared to native myoglobin depends on the degree of glycation: physiological conditions decreased proteasomal degradation whereas moderate glycation increased degradation. Severe glycation again decreased proteolytic cleavage which might be due to crosslinking of protein monomers. The activity of the proteasomal subunit beta 5 is influenced by the presence of glycated myoglobin. In conclusion, the role of the proteasome in the degradation of glycated proteins is highly dependent on the level of glycation and consequent protein unfolding.},
  language  = {en}
}