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	Hypoxia stabilizes the H2 O2 -producing oxidase Nox4 in cardiomyocytes via suppressing autophagy-related lysosomal degradation.
掲載誌名	正式名：Genes to cells : devoted to molecular & cellular mechanisms 略　 称：Genes Cells ISSNコード：13652443/13569597
掲載区分	国外
著者・共著者	Shogo Matsunaga, Akira Kohda, Sachiko Kamakura, Junya Hayase, Kei Miyano, Akira Shiose, Hideki Sumimoto
発行年月	2023/11
概要	The hydrogen peroxide (H2 O2 )-producing NADPH oxidase Nox4, forming a heterodimer with p22phox , is expressed in a variety of cells including those in the heart to mediate adaptive responses to cellular stresses such as hypoxia. Since Nox4 is constitutively active, H2 O2 production is controlled by its protein abundance. Hypoxia-induced Nox4 expression is observed in various types of cells and generally thought to be regulated at the transcriptional level. Here we show that hypoxia upregulates the Nox4 protein level and Nox4-catalyzed H2 O2 production without increasing the Nox4 mRNA in rat H9c2 cardiomyocytes. In these cells, the Nox4 protein is stabilized under hypoxic conditions in a manner dependent on the presence of p22phox . Cell treatment with the proteasome inhibitor MG132 results in a marked decrease of the Nox4 protein under both normoxic and hypoxic conditions, indicating that the proteasome pathway does not play a major role in Nox4 degradation. The decrease is partially restored by the autophagy inhibitor 3-methyladenine. Furthermore, the Nox4 protein level is upregulated by the lysosome inhibitors bafilomycin A1 and chloroquine. Thus, in cardiomyocytes, Nox4 appears to be degraded via an autophagy-related pathway, and its suppression by hypoxia likely stabilizes Nox4, leading to upregulation of Nox4-catalyzed H2 O2 production.
DOI	10.1111/gtc.13085
PMID	37985134