Novel effects and mechanisms of action of heme and soy isoflavones
Project/Area Number |
16500503
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Eating habits, studies on eating habits
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Research Institution | Kanazawa University (2005) Tohoku University (2004) |
Principal Investigator |
OGAWA Kazuhiro Kanazawa University, Graduate School of Medical Science, Associate Professor, 医学系研究科, 助教授 (30344659)
|
Co-Investigator(Kenkyū-buntansha) |
武田 和久 東北大学, 大学院・医学系研究科, 助手 (30311559)
|
Project Period (FY) |
2004 – 2005
|
Project Status |
Completed (Fiscal Year 2005)
|
Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
|
Keywords | heme oxygenase / heme iron / heme / isoflavone / polyamine / 生体防御 |
Research Abstract |
Heme is widely used as a food chemical for iron supplementation. Heme is an essential molecule for us as prosthetic groups for hemoglobin and many other hemoproteins. Excess free heme is a pro-oxidant and toxic, and is degraded by heme oxygenase (HO) to iron, CO and biliverdin, which is rapidly converted to bilirubin, an antroxidant. There are two isozymes of HO, namely inducible HO-1 and constitutive 110-2. Induction of HO-1 is an important defense mechanism against oxidative stress, and some HO inhibitors have antitumor activity. In this project, I have been evalutated the effects and analyzed the mechanisms of action of food chemicals such as heme iron and soy isoflavones on heme catabolism, using various types of human cells. Prolonged hypoxia decreased the expression level of HO-2 as well as that of HO-1, and these down-regulations of HOs were caused at both transcriptional and post-transcriptional levels. Down-regulation of 110-2 by siRNA induced the HO-1 expression, and HO-2 knock-down 1 under some conditions increased the intracellular heme content, suggesting the significance of HO-2 in the maintenance of cellular heme levels and in the regulation of HO-1 expression. Genistein, a soy isoflavone, inhibited the induction of HO-1 by heme and other chemicals, while daidzein, another soy isoflavone, did not inhibited the induction of HO-1 in some cases. Together with results of our other experiments, these inhibitory effects of isoflavones on HO-1 induction were suggested to be mediated by estrogen receptor-independent mechanism.
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Report
(4 results)
Research Products
(13 results)