@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}
}