栀子苷对大鼠肝细胞谷胱甘肽S-转移酶亚基表达的差异诱导作用。

Differential induction of the expression of GST subunits by geniposide in rat hepatocytes.

作者信息

Kuo Wu-Hsien, Wang Chau-Jong, Young Shun-Chieh, Sun Yuan-Chang, Chen Yi-Jun, Chou Fen-Pi

机构信息

Division of Gastroenterology, Department of Internal Medicine, Armed Forces Taichung General Hospital, Taichung, Taiwan.

出版信息

Pharmacology. 2004 Jan;70(1):15-22. doi: 10.1159/000074238.

DOI:10.1159/000074238

PMID:14646352

Abstract

Geniposide, an iridoid glycoside isolated from the fruit of Gardenia jasminoides Ellis, has the biological capabilities of detoxication, antioxidation, and anticarcinogenesis. In this study, the mechanism of geniposide affecting the GST (glutathione S-transferase) system was investigated. Primary cultured rat hepatocytes were treated with geniposide and examined for total GST activity and expression of GST subunits. The results showed that the geniposide-induced GST activity was dose and time dependent. Western blotting data demonstrated that geniposide induced increased protein levels of GSTM1 and GSTM2 (approximately 1.7- and 1.8-fold of control, respectively), but did not increase those of GSTA1. The corresponding transcripts levels were confirmed by RT-PCR. Using PD98059, the effect of geniposide was verified to be via the MEK pathway. The results suggest that geniposide possesses a potential for detoxication by inducing GST activity via increasing the transcription of GSTM1 and GSTM2.

摘要

栀子苷是从栀子果实中分离得到的一种环烯醚萜苷，具有解毒、抗氧化和抗癌的生物学功能。在本研究中，对栀子苷影响谷胱甘肽S-转移酶（GST）系统的机制进行了研究。用栀子苷处理原代培养的大鼠肝细胞，并检测其总GST活性和GST亚基的表达。结果表明，栀子苷诱导的GST活性呈剂量和时间依赖性。蛋白质印迹数据表明，栀子苷诱导GSTM1和GSTM2的蛋白质水平升高（分别约为对照的1.7倍和1.8倍），但未增加GSTA1的蛋白质水平。通过逆转录-聚合酶链反应（RT-PCR）证实了相应的转录本水平。使用PD98059，证实栀子苷的作用是通过丝裂原活化蛋白激酶/细胞外信号调节激酶（MEK）途径实现的。结果表明，栀子苷具有通过增加GSTM1和GSTM2的转录来诱导GST活性从而实现解毒的潜力。