A novel superoxide-producing NAD(P)H oxidase in kidney

Akira Shiose, Junya Kuroda, Kazuhiko Tsuruya, Momoki Hirai, Hideki Hirakata, Seiji Naitoi, Masahira Hattori, Yoshiyuki Sakaki, Hideki Sumimoto

研究成果: Article

404 引用 (Scopus)

抜粋

During phagocytosis, gp91phox, the catalytic subunit of the phagocyte NADPH oxidase, becomes activated to produce superoxide, a precursor of microbicidal oxidants. Currently increasing evidence suggests that nonphagocytic cells contain similar superoxide-producing oxidases, which are proposed to play crucial roles in various events such as cell proliferation and oxygen sensing for erythropoiesis. Here we describe the cloning of human cDNA that encodes a novel NAD(P)H oxidase, designated NOX4 . The NOX4 protein of 578 amino acids exhibits 39% identity to gp91phox with special conservation in membrane-spanning regions and binding sites for heine, FAD, and NAD(P)H, indicative of its function as a superoxide-producing NAD(P)H oxidase. The membrane fraction of kidney-derived human embryonic kidney (HEK) 293 cells, expressing NOX4, exhibits NADH- and NADPH-dependent superoxide-producing activities, both of which are inhibited by diphenylene iodonium, an agent known to block oxygen sensing, and decreased in cells expressing antisense NOX4 mRNA. The human NOX4 gene, comprising 18 exons, is located on chromosome 11q14.2-q21, and its expression is almost exclusively restricted to adult and fetal kidneys. In human renal cortex, high amounts of the NOX4 protein are present in distal tubular cells, which reside near erythropoietin-producing cells. In addition, overexpression of NOX4 in cultured cells leads to increased superoxide production and decreased rate of growth. The present findings thus suggest that the novel NAD(P)H oxidase NOX4 may serve as an oxygen sensor and/or a regulator of cell growth in kidney.

元の言語English
ページ(範囲)1417-1423
ページ数7
ジャーナルJournal of Biological Chemistry
276
発行部数2
DOI
出版物ステータスPublished - 2001 1 12
外部発表Yes

    フィンガープリント

ASJC Scopus subject areas

  • Biochemistry

これを引用

Shiose, A., Kuroda, J., Tsuruya, K., Hirai, M., Hirakata, H., Naitoi, S., Hattori, M., Sakaki, Y., & Sumimoto, H. (2001). A novel superoxide-producing NAD(P)H oxidase in kidney. Journal of Biological Chemistry, 276(2), 1417-1423. https://doi.org/10.1074/jbc.M007597200