Gallate, the component of HIF-inducing catechins, inhibits HIF prolyl hydroxylase
- Department of Thoracic and Cardiovascular Surgery, Osaka Medical College, Daigakumachi, Takatsuki 569-8686 (Japan)
- Department of Biochemistry, Osaka Medical College, Daigakumachi, Takatsuki 569-8686 (Japan)
- Department of Anesthesia, Kyoto University Hospital, Kyoto University, Sakyo-ku, Kyoto 606-8507 (Japan)
- Department of Chemistry, Osaka Medical College, Daigakumachi, Takatsuki 569-8686 (Japan)
Catechins have recently been reported to increase the cellular content of the hypoxia-inducible factor (HIF)-1{alpha} within mammalian cells. These catechins have a gallate moiety as a common structure. We now report that n-propyl gallate (nPG) also increases the HIF-1{alpha} protein in the rat heart-derived H9c2 cells. The increase was dose-dependent and reached a maximum at 2-4 h after the addition of nPG to the cells. nPG did not change the HIF-1{alpha} mRNA level, showing that the increase is a posttranscriptional event. Although nPG did not inhibit the HIF prolyl hydroxylase, gallate, the hydrolysis product of nPG, inhibited the enzyme completely at submillimolar concentrations. Model building studies on the human HIF prolyl hydroxylase 2 showed that the two phenolate oxygen atoms of gallate form a chelate with the active site Fe{sup 2+}, while the carboxyl group of gallate forms a strong ionic/hydrogen bonding interaction with Arg383, explaining why nPG, which has an esterified carboxyl group, is unable to inhibit the hydroxylase. Together with the observation that gallate was detected in the H9c2 cells treated with nPG, these results suggest that nPG incorporated into the cells is hydrolyzed and the released gallate inhibits the HIF prolyl hydroxylase, thereby reducing the HIF degradation rate and increasing the HIF-1{alpha} content.
- OSTI ID:
- 20857910
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 351, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2006.10.025; PII: S0006-291X(06)02260-1; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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