화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.275, No.3, 789-794, 2000
Thiol antioxidant, N-acetylcysteine, activates extracellular signal-regulated kinase signaling pathway in articular chondrocytes
Reactive oxygen species (ROS) generated during inflammation and aging contribute to the resorption of articular cartilage. Low antioxidant levels are a risk factor for arthritis because they protect cartilage from ROS, N-Acetylcysteine (NAC) is a ROS scavenger and, depending upon the concentration, an anti-inflammatory or prooxidant agent. Mechanisms of action for NAC were studied in primary human and bovine chondrocytes, NAC dose-dependently activated phosphorylation of extracellular signal-regulated kinases-mitogen-acivated protein kinases (ERK-MAPK), ERK activation peaked within 15 min and declined afterward up to 180 min. This activation was inhibited by the MAPKK inhibitor, PD098059. The induction was mimicked by other thiols, L-cysteine, reduced glutathione, and pyrrolidine dithiocarbamate (PDTC) but not by a nonthiol, N-acetylalanine. The total nonphosphorylated ERKs levels remained unaffected by these treatments. Activation of the ERK-MAPK pathway provides a mechanism for the reported promotion of chondrocyte survival by thiol antioxidants,