4-O-Methylascochlorin inhibits the prolyl hydroxylation of hypoxia-inducible factor-1α, which is attenuated by ascorbate View Full Text


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Article Info

DATE

2019-05

AUTHORS

Tetsuya Kondo, Kenji Takeda, Ryo Muko, Akihiro Ito, Young-Chae Chang, Junji Magae, Takao Kataoka

ABSTRACT

4-O-Methylascochlorin (MAC), a methylated derivative of ascochlorin, was previously shown to promote the accumulation of hypoxia-inducible factor (HIF)-1α 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-1α in human fibrosarcoma HT-1080 cells. MAC promoted the accumulation of the HIF-1α 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-1α accumulation. MAC-induced increases in HIF-1α transcriptional activity were also attenuated by ascorbate. MAC inhibited the hydroxylation of HIF-1α 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-1α by preventing prolyl hydroxylation, and ascorbate attenuated the MAC-mediated inhibition of HIF-1α prolyl hydroxylation. More... »

PAGES

1-11

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41429-019-0157-0

    DOI

    http://dx.doi.org/10.1038/s41429-019-0157-0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112308254

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30796332


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