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Title 

N-acetylcysteine induces cell cycle arrest in hepatic stellate cells through its reducing activity

Authors 

Ki Yong KimTai Youn RhimIn Pyo ChoiSoung Soo Kim

Publisher 

American Society for Biochemistry and Molecular Biology

Issue Date 

2001

Citation 

Journal of Biological Chemistry, vol. 276, no. 44, pp. 40591-40598

Keywords 

antioxidantsbiological organsenzymesoxidationredox reactionssignaling pathwaycells2 (2 amino 3 methoxyphenyl)chromoneacetylcysteinecollagen type 1

Abstract 

Activation of hepatic stellate cells (HSC) has been identified as a critical step in hepatic fibrogenesis and is regulated by several factors including cytokines and oxidative stress. However, the molecular mechanism for HSC inactivation is not well understood. We investigated an N-acetyl-L-cysteine (NAC)-mediated signaling pathway involved in HSC inactivation. NAC, which acting through its reducing activity, induced cell arrest at G1 via the mitogen-activated protein kinase (MAPK) kinase (MEK)/MAPK pathway in a Ras-independent manner. The sustained activation of this extracellular signal-regulated kinase induced the expression of p21Cip1/WAF1, a cell cycle-dependent kinase inhibitor, and mediated cell growth arrest through the Sp1 transcription activator-dependent mechanism. These effects of NAC were all reversed by treatment of HSC with MEK inhibitor PD98059 followed by culturing HSC on type I collagen-coated flasks. The collagen-mediated suppression of NAC-induced arrest may be due to an overriding of the cell cycle arrest through an acceleration of integrin-induced cell growth. NAC action is actually dependent on modulating the redox states of cysteine residues of target proteins such as Raf-1, MEK, and ERK. In conclusion, an understanding of the NAC signaling pathway in HSC should provide the theoretical basis for clinical approaches using antioxidant therapies in liver fibrosis.

ISSN 

0021-9258

Link 

http://dx.doi.org/10.1074/jbc.M100975200

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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