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  -