This article is part of the supplement: 11th International Symposium on the Cells of the Hepatic Sinusoid and their Relation to Other Cells

Proceedings

Amino acids, L-Cysteine and L-Methionine, Attenuate Activation of Rat Stellate Cells in Primary Culture

Hiroko Matsui^1,2 , Tokuko Takashima¹ , Naoto Maeda¹ , Yukihiro Imanishi¹ , Naoki Uyama³ , Hiroaki Okuyama³ and Norifumi Kawada¹

¹Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan

²Minophagen Pharmaceutical Company, Osaka, Japan

³Department of Gastroenterological Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Comparative Hepatology 2004, 3(Suppl 1):S9doi:10.1186/1476-5926-2-S1-S9

Published:	14 January 2004

First paragraph (this article has no abstract)

Regulation of hepatic stellate cell activation is currently one of the focuses of clinical investigation in order to establish a useful therapeutic strategy for liver fibrosis. Because oxidative stress caused at the inflammatory site and reactive oxygen species derived from damaged hepatocytes has been thought to pull the trigger for the cell activation, it is reasonable to speculate that antioxidative substances are promising to attenuate the activation process. In fact, alpha-tocopherol and natural flavonoids have potential to inhibit collagen gene expression and DNA synthesis of stellate cells, respectively. Our laboratory demonstrated that N-acetyl-L-cysteine (NAC) inhibits DNA synthesis of rat stellate cells in response to serum and PDGF-BB [1]. NAC was found to downregulate the expression of PDGF receptor beta PDGFR beta), thereby hampering PDGF-BB-dependent phosphorylation of MAP kinase and Akt [2,3]. In addition, Kim et al. [4] reported that NAC induces cell cycle arrest at G1 phase through inducing p21. Suppression of dimethylnitrosamine-induced liver fibrosis by NAC was also reported. Taken together, these results suggested that reducing compounds with -SH suppliers would be promising candidates attenuating the activation of stellate cells in culture and also in vivo.