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Resveratrol strongly enhances the retinoic acid-induced superoxide generating activity via up-regulation of gp91-phox gene expression in U937 cells

The membrane bound cytochrome b558 composed of gp91-phox and p22-phox proteins, and cytosolic proteins p40-, p47-and p67-phox are important components of superoxide (O2−)-generating system in phagocytes. Here, we describe that resveratrol, a pleiotropic phytochemical belonging to the stilbenoids, dr...

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Published in:Biochemical and biophysical research communications 2018-01, Vol.495 (1), p.1195-1200
Main Authors: Kikuchi, Hidehiko, Mimuro, Hitomi, Kuribayashi, Futoshi
Format: Article
Language:English
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Summary:The membrane bound cytochrome b558 composed of gp91-phox and p22-phox proteins, and cytosolic proteins p40-, p47-and p67-phox are important components of superoxide (O2−)-generating system in phagocytes. Here, we describe that resveratrol, a pleiotropic phytochemical belonging to the stilbenoids, dramatically activates the O2−-generating system during retinoic acid (RA)-induced differentiation of human monoblastic leukemia U937 cells to macrophage-like cells. When U937 cells were cultured in the presence of RA and resveratrol, the O2−-generating activity increased more than 5-fold compared with that in the absence of the latter. Semiquantitative RT-PCR showed that co-treatment with RA and resveratrol strongly enhanced transcription of the gp91-phox compared with those of the RA-treatment only. On the other hand, immunoblot analysis revealed that co-treatment with RA and resveratrol caused remarkable accumulation of protein levels of gp91-phox (to 4-fold), p22-phox (to 5-fold) and p47-phox (to 4-fold) compared with those of the RA-treatment alone. In addition, ChIP assay suggested that resveratrol participates in enhancing the gene expression of gp91-phox via promoting acetylation of Lys-9 residues and Lys-14 residues of histone H3 within chromatin around the promoter regions of the gene. These results suggested that resveratrol strongly enhances the RA-induced O2−-generating activity via up-regulation of gp91-phox gene expression in U937 cells. •Resveratrol effectively enhanced the RA-induced O2−-generating activity.•Resveratrol strongly enhanced gene expression of gp91-phox.•Resveratrol caused remarkable accumulation of cytochrome b558 and p47-phox proteins.•Resveratrol promoted histone acetylation around the promoter of gp91-phox gene.•Resveratrol enhances the O2−-generating activity via transactivation of gp91-phox.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2017.11.161