ミヤノ　ケイ   Kei Miyano   宮野　佳    所属   川崎医科大学  医学部 一般教養　自然科学    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	The downregulation of NADPH oxidase Nox4 during hypoxia in hemangioendothelioma cells: a possible role of p22phox on Nox4 protein stability.
掲載誌名	正式名：Free Radical Research 略　 称：Free Radic Res ISSNコード：10715762/10292470
掲載区分	国外
巻・号・頁	55(9-10),pp.996-1004
総ページ数	9
著者・共著者	Miyano K, Okamoto S, Yamauchi A, Kawai C, Kajikawa M, Kiyohara T, Itsumi M, Taura M, Kuribayashi F.
担当区分	筆頭著者,責任著者
発行年月	2022/01/11
概要	NADPH oxidase (Nox) 4 produces H2O2 by forming a heterodimer with p22phox and is involved in hemangioendothelioma development through monocyte chemoattractant protein-1 (MCP-1) upregulation. Here, we show that Nox4 protein levels were maintained by p22phox in hemangioendothelioma cells and Nox4 protein stability was dependent on p22phox coexpression. Conversely, the degradation of Nox4 monomer was enhanced by p22phox knockdown. Under hypoxic conditions in hemangioendothelioma cells, p22phox was downregulated at the mRNA and protein levels. Downregulation of p22phox 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 p22phox 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 p22phox depletion. MCP-1 secretion was decreased concurrently with hypoxia-induced Nox4 downregulation compared with that under normoxia.