Thiol antioxidant, N-acetylcysteine, activates extracellular signal-regulated kinase signaling pathway in articular chondrocytes.

Abstract:

: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.

authors

Li WQ,Dehnade F,Zafarullah M

doi

10.1006/bbrc.2000.3385

subject

Has Abstract

pub_date

2000-09-07 00:00:00

pages

789-94

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(00)93385-0

journal_volume

275

pub_type

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