Specific induction of glutathione S-transferase GSTM2 subunit expression by epigallocatechin gallate in rat liver.
The antitumor effect of green tea polyphenols has been well characterized in numerous papers. However, the mechanism of their action is still poorly defined. In this study, epigallocatechin gallate (EGCG), the main ingredient of green tea extract, was studied for its effect on the expression of glutathione S-transferases (GSTs) in rat liver to examine the mechanism of action. Liver samples were collected from Sprague-Dawley rats treated with EGCG in H(2)O by portal vein perfusion and examined for total GST activity and GST expression. The results showed that the induction of GST activity by EGCG was dose- and time-dependent. GST activity was increased about 28-fold at 12 hr after treatment. Three GST subunits (GSTA1/2, GSTM1, and GSTM2) were examined by Western blot for changes in protein level affected by EGCG (1 mg/kg weight). Only GSTM2 revealed a significant time-dependent increase, with a maximal induction of approximately 2.0-fold. The differential effect of EGCG on GST subunit expression was also verified by immunocytochemical examination and showed strong induction of the GSTM2 (but not the GSTA1/2 and GSTM1) level in liver section. This induction occurred as early as 3 hr after treatment and extended gradually outward from the hepatic veins as treatment time increased. The change in the GSTM2 protein level was accompanied by a corresponding alteration in mRNA quantity ( approximately 2.0-fold of control). Our report is the first to demonstrate a specific induction of the GSTM2 subunit by a chemopreventor and suggests a primary influence of EGCG on GSTM2 gene expression.
Chou
F P
FP
Institute of Biochemistry, Chung Shan Medical and Dental College, Taichung, Taiwan.
Chu
Y C
YC
Hsu
J D
JD
Chiang
H C
HC
Wang
C J
CJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004790:Enzyme Induction; D015870:Gene Expression / Q000187:drug effects; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000235:genetics; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000970:Antineoplastic Agents; D007527:Isoenzymes; D012333:RNA, Messenger; D002392:Catechin; C045651:epigallocatechin gallate; D005982:Glutathione Transferase