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标题：Antiproliferative and Proapoptotic Effects of Tocopherol and Tocol on Activated Hepatic Stellate Cells
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作者：Noriko YAMAGUCHI ; Yoshihiro MEZAKI ; Mitsutaka MIURA 等
期刊名称：Journal of Nutritional Science and Vitaminology
印刷版ISSN：0301-4800
电子版ISSN：1881-7742
出版年度：2011
卷号：57
期号：5
页码：317-325
DOI：10.3177/jnsv.57.317
出版社：Center for Academic Publications Japan
摘要：Activated hepatic stellate cells (HSCs) play crucial roles in liver fibrosis. In the course of liver injury, HSCs, which reside in perisinusoidal spaces and lose lipid droplets, morphologically change into a myofibroblastic phenotype and acquire an increased proliferation activity in what is known as the activated state. We have investigated therapeutic strategies for liver fibrosis by promoting spontaneous reversion or inducing apoptosis in activated HSCs. Vitamin E consists of four tocopherols and four tocotrienols, all of which are well-known antioxidants. In this study, the antiproliferative and proapoptotic effects of a tocol, which lacks methyl groups attached to the chromanol ring, and four tocopherols were investigated using activated HSCs. δ-Tocopherol and tocol exhibited relatively high proliferation inhibitory and proapoptotic abilities. However, they did not show proliferation inhibition ability on primary hepatocytes or HepG2 cells. Significant cell detachment was also observed in δ-tocopherol- and tocol-treated HSCs. Decreased protein expressions of α-smooth muscle actin and β1 integrin were observed in a dose-dependent manner. These results indicate that δ-tocopherol and tocol induce anoikis in activated HSCs.
关键词：tocopherol;tocol;hepatic stellate cells;apoptosis;anoikis