Roles of heme oxygenase-1 in curcumin-induced growth inhibition in rat smooth muscle cells

被引:75
作者
Pae, Hyun-Ock
Jeong, Gil-Saeng
Jeong, Sun-Oh
Kim, Hak Sung
Kim, Soon-Ai
Kim, Youn-Chul
Yoo, Su-Jin
Kim, Heung-Doo
Chung, Hun-Taeg [1 ]
机构
[1] Wonkwang Univ, Sch Med, Med Resources Res Inst, Iksan 570749, South Korea
[2] Wonkwang Univ, Sch Med, Dept Microbiol & Immunol, Iksan 570749, South Korea
[3] Wonkwang Univ, Sch Med, Dept Emergency, Iksan 570749, South Korea
[4] Wonkwang Univ, Coll Pharm, Iksan 570749, South Korea
[5] Wonkwang Univ, Profess Grad Sch Oriental Med, Iksan 570749, South Korea
[6] Sohae Coll, Dept Clin Pathol, Gunsan 573717, South Korea
关键词
carbon monoxide; cell proliferation; curcumin; heme oxygenase-1; NF-E2-related factor 2; muscle; smooth; vascular; CYCLE PROGRESSION; CARBON-MONOXIDE; NRF2; TETRAHYDROCURCUMIN; PROLIFERATION; ACTIVATION; GENE; INVOLVEMENT; EXPRESSION; INDUCTION;
D O I
10.1038/emm.2007.30
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In vascular smooth muscle cells (VSMCs), induction of the heme oxygenase-1 (HO-1) confers vascular protection against cellular proliferation mainly via its up-regulation of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) that is involved in negative regulation of cellular proliferation. In the present study, we investigated whether the phytochemical curcumin and its metabolite tetrahydrocurcumin could induce HO-1 expression and growth inhibition in rat VSMCs and, if so, whether their antiproliferative effect could be mediated via HO-1 expression. At non-toxic concentrations, curcumin possessing two Michael-reaction acceptors induced HO-1 expression by activating antioxidant response element (ARE) through translocation of the nuclear transcription factor E2-related factor-2 (Nrf2) into the nucleus and also inhibited VSMC growth triggered by 5% FBS in a dose-dependent manner. In contrast, tetrahydrocurcumin lacking Michael-reaction acceptor showed no effect on HO-1 expression, ARE activation and VSMC growth inhibition. The antiproliferative effect of curcumin in VSMCs was accompanied by the increased expression of p21(WAF1/CIP1). Inhibition of VSMC growth and expression of p21WAF1/CIP1 by curcumin were partially, but not completely, abolished when the cells were coincubated with the HO inhibitor tin protoporphyrin. In human aortic smooth muscle cells (HASMCs), curcumin also inhibited growth triggered by TNF-alpha and increased p21(WAF1/CIP1) expression via HO-1-dependent manner. Our findings suggest that curcumin has an ability to induce HO-1 expression, presumably through Nrf2-dependent ARE activation, in rat VSMCs and HASMCs, and provide evidence that the antiproliferative effect of curcumin is considerably linked to its ability to induce HO-1 expression.
引用
收藏
页码:267 / 277
页数:11
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