Document Detail


A novel superoxide-producing NAD(P)H oxidase in kidney.
MedLine Citation:
PMID:  11032835     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
During phagocytosis, gp91(phox), 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 gp91(phox) with special conservation in membrane-spanning regions and binding sites for heme, 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.
Authors:
A Shiose; J Kuroda; K Tsuruya; M Hirai; H Hirakata; S Naito; M Hattori; Y Sakaki; H Sumimoto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  276     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-03-06     Completed Date:  2001-04-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1417-23     Citation Subset:  IM    
Affiliation:
Department of Molecular and Structural Biology, Kyushu University Graduate School of Medical Science, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/AB041035
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MeSH Terms
Descriptor/Qualifier:
Adult
Amino Acid Sequence
Bacterial Proteins*
Cell Line
Chromosome Mapping
Chromosomes, Human, Pair 11*
Cloning, Molecular
Exons
Expressed Sequence Tags
Fetus
Gene Expression Regulation, Developmental
Gene Expression Regulation, Enzymologic
Humans
In Situ Hybridization, Fluorescence
Karyotyping
Kinetics
Molecular Sequence Data
NADH, NADPH Oxidoreductases / chemistry
NADPH Oxidase / chemistry,  genetics*,  metabolism*
Organ Specificity
RNA, Messenger / genetics
Recombinant Proteins / metabolism
Sequence Alignment
Sequence Homology, Amino Acid
Superoxides / metabolism
Transfection
Chemical
Reg. No./Substance:
0/Bacterial Proteins; 0/RNA, Messenger; 0/Recombinant Proteins; 11062-77-4/Superoxides; EC 1.6.-/NADH, NADPH Oxidoreductases; EC 1.6.3.-/NOX4 protein, human; EC 1.6.3.1/NADPH Oxidase; EC 1.6.99.-/NADPH oxidase 1; EC 1.6.99.-/Nox-2 protein, bacteria

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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