Sunday November 19th 2017

Dimethyl fumarate inhibits the expression and function of hypoxia-inducible factor-1α (HIF-1α).

In this study, we found that DMF inhibited hypoxia- induced expression of HIF-1α and its target genes such as interleukin 8 (IL-8) and vascular endothelial growth factor (VEGF) in MC3T3 E1 cells. Mechanistically, DMF promoted HIF-1α degradation in a proteasome-dependent but von Hippel-Lindau (VHL) protein-independent manner. Importantly, we found that DMF disrupted the interaction between HIF-1α and its chaperone heat shock protein 90 (Hsp90) but promoted the interaction between HIF-1α and the receptor of activated protein kinase C (RACK1). These data suggest that DMF might promote degradation of HIF-1α by affecting its folding and maturation. Based on these observations, we conclude that DMF is a novel inhibitor of HIF-1α. PMID: 24569076 [PubMed – as supplied by publisher] (Sour…

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Dimethyl fumarate inhibits the expression and function of hypoxia-inducible factor-1α (HIF-1α).

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