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A novel superoxide-producing NAD(P)H oxidase in kidney
A Shiose1, J Kuroda, K Tsuruya
1Department of Molecular and Structural Biology, Kyushu University Graduate School of Medical Science, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
The Journal of Biological Chemistry
|October 18, 2000
Summary
Researchers identified a new enzyme, NOX4, involved in superoxide production. This novel NAD(P)H oxidase is primarily found in the kidney and may regulate cell growth and oxygen sensing.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Phagocytosis involves gp91(phox) in superoxide production.
- Nonphagocytic cells may possess similar oxidases for cell proliferation and oxygen sensing.
- The role of novel NAD(P)H oxidases in cellular functions is increasingly recognized.
Purpose of the Study:
- To clone and characterize a novel human NAD(P)H oxidase.
- To investigate the function and localization of the newly identified NOX4 enzyme.
- To explore the potential roles of NOX4 in kidney physiology.
Main Methods:
- Human cDNA cloning and sequencing of NOX4.
- Expression of NOX4 in HEK 293 cells and measurement of superoxide production.
- Analysis of NOX4 gene location and expression patterns.
- Assessment of NOX4's effect on cell growth and superoxide levels.
Main Results:
- Cloned human NOX4 cDNA encoding a 578-amino acid protein with homology to gp91(phox).
- NOX4-expressing cells showed NADH/NADPH-dependent superoxide production inhibited by diphenylene iodonium.
- NOX4 gene located on chromosome 11q14.2-q21, with expression predominantly in kidneys.
- NOX4 overexpression increased superoxide production and decreased cell growth.
Conclusions:
- NOX4 is a novel superoxide-producing NAD(P)H oxidase.
- NOX4 is highly expressed in kidney distal tubular cells.
- NOX4 may function as an oxygen sensor and/or regulator of cell growth in the kidney.