Cited 139 time in
- Title
- N-acetylcysteine induces cell cycle arrest in hepatic stellate cells through its reducing activity
- Author(s)
- Ki Yong Kim; Tai Youn Rhim; In Pyo Choi; Soung Soo Kim
- Bibliographic Citation
- Journal of Biological Chemistry, vol. 276, no. 44, pp. 40591-40598
- Publication Year
- 2001
- 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
- Publisher
- Amer Soc Biochemistry Molecular Biology Inc
- DOI
- http://dx.doi.org/10.1074/jbc.M100975200
- Type
- Article
- Appears in Collections:
- Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
- Files in This Item:
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