Dataset Information

Hydrogen sulfide inhibits the translational expression of hypoxia-inducible factor-1?.

ABSTRACT:

Background and purpose

The accumulation of hypoxia-inducible factor-1? (HIF-1?) is under the influence of hydrogen sulfide (H(2) S), which regulates hypoxia responses. The regulation of HIF-1? accumulation by H(2) S has been shown, but the mechanisms for this effect are largely elusive and controversial. This study aimed at addressing the controversial mechanisms for and the functional importance of the interaction of H(2) S and HIF-1? protein.

Experimental approach

HIF-1? protein levels and HIF-1? transcriptional activity were detected by Western blotting and luciferase assay. The mechanisms for H(2) S-regulated HIF-1? protein levels were determined using short interfering RNA transfection, co-immunoprecipitation and 7-methyl-GTP sepharose 4B pull-down assay. Angiogenic activity was evaluated using tube formation assay in EA.hy926 cells.

Key results

The accumulation of HIF-1? protein under hypoxia (1% O(2) ) or hypoxia-mimetic conditions was reversed by sodium hydrosulfide (NaHS). This effect of NaHS was not altered after blocking the ubiquitin-proteasomal pathway for HIF-1? degradation; however, blockade of protein translation with cycloheximide abolished the effect of NaHS on the half-life of HIF-1? protein. Knockdown of eukaryotic translation initiation factor 2? (eIF2?) suppressed the effect of NaHS on HIF-1? protein accumulation under hypoxia. NaHS inhibited the expression of VEGF under hypoxia. It also decreased in vitro capillary tube formation and cell proliferation of EA.hy926 cells under hypoxia, but stimulated the tube formation under normoxia.

Conclusions and implications

H(2) S suppresses HIF-1? translation by enhancing eIF2? phosphorylation under hypoxia. The interaction of H(2) S and HIF-1? inhibits the angiogenic activity of vascular endothelial cells under hypoxia through the down-regulation of VEGF.

SUBMITTER: Wu B

PROVIDER: S-EPMC3514762 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Publications

Hydrogen sulfide inhibits the translational expression of hypoxia-inducible factor-1α.

Wu Bo B Teng Huajian H Yang Guangdong G Wu Lingyun L Wang Rui R

British journal of pharmacology 20121201 7

<h4>Background and purpose</h4>The accumulation of hypoxia-inducible factor-1α (HIF-1α) is under the influence of hydrogen sulfide (H(2) S), which regulates hypoxia responses. The regulation of HIF-1α accumulation by H(2) S has been shown, but the mechanisms for this effect are largely elusive and controversial. This study aimed at addressing the controversial mechanisms for and the functional importance of the interaction of H(2) S and HIF-1α protein.<h4>Experimental approach</h4>HIF-1α protein ...[more]

PMID: 22831549

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