%0 Journal Article
%T 4-O-Methylascochlorin inhibits the prolyl hydroxylation of hypoxia-inducible factor-1¦Á, which is attenuated by ascorbate
%J -
%D 2019
%R https://doi.org/10.1038/s41429-019-0157-0
%X 4-O-Methylascochlorin (MAC), a methylated derivative of ascochlorin, was previously shown to promote the accumulation of hypoxia-inducible factor (HIF)-1¦Á in human breast adenocarcinoma MCF-7 cells. In the present study, we further investigated the effects of MAC on the expression and function of HIF-1¦Á in human fibrosarcoma HT-1080 cells. MAC promoted the accumulation of the HIF-1¦Á protein without affecting its constitutive mRNA expression and augmented the transcriptional activation of HIF target genes. Ascorbate, but not N-acetylcysteine, attenuated MAC-mediated HIF-1¦Á accumulation. MAC-induced increases in HIF-1¦Á transcriptional activity were also attenuated by ascorbate. MAC inhibited the hydroxylation of HIF-1¦Á at the proline 564 residue, while it was reversed by ascorbate. MAC slightly decreased the intracellular concentration of ascorbate. The present results demonstrated that MAC promoted the accumulation of HIF-1¦Á by preventing prolyl hydroxylation, and ascorbate attenuated the MAC-mediated inhibition of HIF-1¦Á prolyl hydroxylation
%U https://www.nature.com/articles/s41429-019-0157-0