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  - 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  -