The downregulation of NADPH oxidase Nox4 during hypoxia in hemangioendothelioma cells: a possible role of p22 phox on Nox4 protein stability

Kei Miyano, Shuichiro Okamoto, Akira Yamauchi, Chikage Kawai, Mizuho Kajikawa, Takuya Kiyohara, Momoe Itsumi, Masahiko Taura, Futoshi Kuribayashi

研究成果: ジャーナルへの寄稿学術誌査読

抄録

NADPH oxidase (Nox) 4 produces H2O2 by forming a heterodimer with p22 phox and is involved in hemangioendothelioma development through monocyte chemoattractant protein-1 (MCP-1) upregulation. Here, we show that Nox4 protein levels were maintained by p22 phox in hemangioendothelioma cells and Nox4 protein stability was dependent on p22 phox coexpression. Conversely, the degradation of Nox4 monomer was enhanced by p22 phox knockdown. Under hypoxic conditions in hemangioendothelioma cells, p22 phox was downregulated at the mRNA and protein levels. Downregulation of p22 phox protein resulted in the enhanced degradation of Nox4 protein in hypoxia-treated hemangioendothelioma cells. In contrast, Nox2, a Nox isoform, was not altered at the protein level under hypoxic conditions. Nox2 exhibited a higher affinity for p22 phox compared with Nox4, suggesting that when coexpressed with Nox4 in the same cells, Nox2 acts as a competitor. Nox2 knockdown restored Nox4 protein levels partially reduced by hypoxic treatment. Thus, Nox4 protein levels were attenuated in hypoxia-treated cells resulting from p22 phox depletion. MCP-1 secretion was decreased concurrently with hypoxia-induced Nox4 downregulation compared with that under normoxia.

本文言語英語
ページ(範囲)996-1004
ページ数9
ジャーナルFree Radical Research
55
9-10
DOI
出版ステータス出版済み - 2021

!!!All Science Journal Classification (ASJC) codes

  • 生化学

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