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

Research output: Contribution to journalArticle

401 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1417-1423
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number2
DOIs
Publication statusPublished - 2001 Jan 12
Externally publishedYes

Fingerprint

NADPH Oxidase
Superoxides
Kidney
NAD
Oxygen
Cells
Membranes
Oxygen sensors
Flavin-Adenine Dinucleotide
Cloning
Cell proliferation
Cell growth
Chromosomes
Erythropoietin
NADP
Oxidants
Erythropoiesis
Phagocytes
Growth
Exons

ASJC Scopus subject areas

  • Biochemistry

Cite this

Shiose, A., Kuroda, J., Tsuruya, K., Hirai, M., Hirakata, H., Naitoi, S., ... 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

A novel superoxide-producing NAD(P)H oxidase in kidney. / Shiose, Akira; Kuroda, Junya; Tsuruya, Kazuhiko; Hirai, Momoki; Hirakata, Hideki; Naitoi, Seiji; Hattori, Masahira; Sakaki, Yoshiyuki; Sumimoto, Hideki.

In: Journal of Biological Chemistry, Vol. 276, No. 2, 12.01.2001, p. 1417-1423.

Research output: Contribution to journalArticle

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, vol. 276, no. 2, pp. 1417-1423. https://doi.org/10.1074/jbc.M007597200
Shiose A, Kuroda J, Tsuruya K, Hirai M, Hirakata H, Naitoi S et al. A novel superoxide-producing NAD(P)H oxidase in kidney. Journal of Biological Chemistry. 2001 Jan 12;276(2):1417-1423. https://doi.org/10.1074/jbc.M007597200
Shiose, Akira ; Kuroda, Junya ; Tsuruya, Kazuhiko ; Hirai, Momoki ; Hirakata, Hideki ; Naitoi, Seiji ; Hattori, Masahira ; Sakaki, Yoshiyuki ; Sumimoto, Hideki. / A novel superoxide-producing NAD(P)H oxidase in kidney. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 2. pp. 1417-1423.
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