Advanced oxidation protein products induce apoptosis of human chondrocyte through reactive oxygen species-mediated mitochondrial dysfunction and endoplasmic reticulum stress pathways.

Abstract

Advanced oxidation production products (AOPPs) have been confirmed to accumulate in patients with rheumatoid arthritis (RA). Previous study demonstrated that AOPPs could accelerate cartilage destruction in rabbit arthritis model. However, the effect of AOPP stimulation on apoptosis of human chondrocyte and the underlying mechanisms remains unclear. This study demonstrated that exposure of chondrocyte to AOPPs resulted in cell apoptosis. AOPP stimulation triggered reactive oxygen species (ROS) production, which induced mitochondrial dysfunction and endoplasmic reticulum stress (ER stress) resulted in caspase activation. Furthermore, an antioxidant, N-acetylcysteine, markedly blocked these signals. Our study demonstrated that AOPPs induce apoptosis via ROS-related mitochondria- and ER-dependent signals in human chondrocyte. Targeting AOPP-triggered ROS generation might be as a promising option for patients with RA.

• Authors: Wenbin Ye, Siyuan Zhu, Congrui Liao, Jun Xiao, Qian Wu, Zhen Lin, Jianting Chen
• Journal: Fundamental & clinical pharmacology (Fundam Clin Pharmacol) Vol. 31 Issue 1 Pg. 64-74 (Feb 2017) ISSN: 1472-8206 [Electronic] England
• PMID: 27483042 (Publication Type: Journal Article)
• Copyright: © 2016 Société Française de Pharmacologie et de Thérapeutique.

Chemical References

• Advanced Oxidation Protein Products
• Reactive Oxygen Species
• Serum Albumin

Topics

• Advanced Oxidation Protein Products (metabolism, pharmacology)
• Aged
• Apoptosis (drug effects)
• Arthritis, Rheumatoid (metabolism, pathology)
• Cell Culture Techniques
• Cells, Cultured
• Chondrocytes (drug effects, metabolism, pathology)
• Endoplasmic Reticulum Stress (drug effects)
• Female
• Humans
• Male
• Middle Aged
• Mitochondria (drug effects, pathology)
• Reactive Oxygen Species (metabolism)
• Serum Albumin (pharmacology)