Refine
Has Fulltext
- no (3) (remove)
Year of publication
- 2018 (3)
Document Type
- Article (3) (remove)
Language
- English (3)
Is part of the Bibliography
- yes (3)
Keywords
- Aging (2)
- Advanced glycation end products (1)
- Apoptosis (1)
- Collagen (1)
- ER stress (1)
- Methylglyoxal (1)
- NZO (1)
- Oxidative stress (1)
- Proteasome and lysosome (1)
- Proteostasis (1)
Institute
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.