NOX4
NADPH oxidase 4 is an enzyme that in humans is encoded by the NOX4 gene, and is a member of the NOX family of NADPH oxidases.[5]
Function
Oxygen sensing is essential for homeostasis in all aerobic organisms. A phagocyte-type oxidase, similar to that responsible for the production of large amounts of reactive oxygen species (ROS) in neutrophil granulocytes, with resultant antimicrobial activity, has been postulated to function in the kidney as an oxygen sensor that regulates the synthesis of erythropoietin in the renal cortex.[5]
Nox4 protects the vasculature against inflammatory stress.[6] Nox-dependent reactive oxygen species modulation by amino endoperoxides can induce apoptosis in high Nox4-expressing cancer cells.[7]
A study found that NOX4 facilitates certain beneficial adaptive responses to exercise mediated by ROS. Moreover, reductions in skeletal muscle NOX4 in aging and obesity was shown to contribute to the development of insulin resistance and may promote oxidative stress.[8]
References
- GRCh38: Ensembl release 89: ENSG00000086991 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000030562 - Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Entrez Gene: NOX4 NADPH oxidase 4".
- Schröder K, Zhang M, Benkhoff S, Mieth A, Pliquett R, Kosowski J, Kruse C, Luedike P, Michaelis UR, Weissmann N, Dimmeler S, Shah AM, Brandes RP (April 2012). "Nox4 is a protective reactive oxygen species generating vascular NADPH oxidase". Circ. Res. 110 (9): 1217–25. doi:10.1161/CIRCRESAHA.112.267054. PMID 22456182.
- Zhu P, Tong BM, Wang R, Chen JP, Foo S, Chong HC, Wang XL, Ang GY, Chiba S, Tan NS (March 2013). "Nox4-dependent ROS modulation by amino endoperoxides to induce apoptosis in cancer cells". Cell Death Dis. 4 (3): e552. doi:10.1038/cddis.2013.68. PMC 3615744. PMID 23519121.
- Xirouchaki, Chrysovalantou E.; Jia, Yaoyao; McGrath, Meagan J.; Greatorex, Spencer; Tran, Melanie; Merry, Troy L.; Hong, Dawn; Eramo, Matthew J.; Broome, Sophie C.; Woodhead, Jonathan S. T.; D’souza, Randall F.; Gallagher, Jenny; Salimova, Ekaterina; Huang, Cheng; Schittenhelm, Ralf B.; Sadoshima, Junichi; Watt, Matthew J.; Mitchell, Christina A.; Tiganis, Tony (December 2021). "Skeletal muscle NOX4 is required for adaptive responses that prevent insulin resistance". Science Advances. 7 (51): eabl4988. Bibcode:2021SciA....7L4988X. doi:10.1126/sciadv.abl4988. PMC 8673768. PMID 34910515.
Further reading
- Lachgar A, Sojic N, Arbault S, et al. (1999). "Amplification of the inflammatory cellular redox state by human immunodeficiency virus type 1-immunosuppressive tat and gp160 proteins". J. Virol. 73 (2): 1447–52. doi:10.1128/JVI.73.2.1447-1452.1999. PMC 103969. PMID 9882350.
- Geiszt M, Kopp JB, Várnai P, Leto TL (2000). "Identification of renox, an NAD(P)H oxidase in kidney". Proc. Natl. Acad. Sci. U.S.A. 97 (14): 8010–4. Bibcode:2000PNAS...97.8010G. doi:10.1073/pnas.130135897. PMC 16661. PMID 10869423.
- Shiose A, Kuroda J, Tsuruya K, et al. (2001). "A novel superoxide-producing NAD(P)H oxidase in kidney". J. Biol. Chem. 276 (2): 1417–23. doi:10.1074/jbc.M007597200. PMID 11032835.
- Cheng G, Cao Z, Xu X, et al. (2001). "Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and Nox5". Gene. 269 (1–2): 131–40. doi:10.1016/S0378-1119(01)00449-8. PMID 11376945.
- Brar SS, Kennedy TP, Sturrock AB, et al. (2002). "An NAD(P)H oxidase regulates growth and transcription in melanoma cells". Am. J. Physiol., Cell Physiol. 282 (6): C1212–24. doi:10.1152/ajpcell.00496.2001. PMID 11997235. S2CID 25900754.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Kalinina N, Agrotis A, Tararak E, et al. (2002). "Cytochrome b558-dependent NAD(P)H oxidase-phox units in smooth muscle and macrophages of atherosclerotic lesions". Arterioscler. Thromb. Vasc. Biol. 22 (12): 2037–43. doi:10.1161/01.ATV.0000040222.02255.0F. PMID 12482831.
- Hilenski LL, Clempus RE, Quinn MT, et al. (2004). "Distinct subcellular localizations of Nox1 and Nox4 in vascular smooth muscle cells". Arterioscler. Thromb. Vasc. Biol. 24 (4): 677–83. doi:10.1161/01.ATV.0000112024.13727.2c. PMID 14670934.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Mahadev K, Motoshima H, Wu X, et al. (2004). "The NAD(P)H oxidase homolog Nox4 modulates insulin-stimulated generation of H2O2 and plays an integral role in insulin signal transduction". Mol. Cell. Biol. 24 (5): 1844–54. doi:10.1128/MCB.24.5.1844-1854.2004. PMC 350558. PMID 14966267.
- Chamulitrat W, Stremmel W, Kawahara T, et al. (2004). "A constitutive NADPH oxidase-like system containing gp91phox homologs in human keratinocytes". J. Invest. Dermatol. 122 (4): 1000–9. doi:10.1111/j.0022-202X.2004.22410.x. PMID 15102091.
- Vaquero EC, Edderkaoui M, Pandol SJ, et al. (2004). "Reactive oxygen species produced by NAD(P)H oxidase inhibit apoptosis in pancreatic cancer cells". J. Biol. Chem. 279 (33): 34643–54. doi:10.1074/jbc.M400078200. PMID 15155719.
- Schwarzer C, Machen TE, Illek B, Fischer H (2004). "NADPH oxidase-dependent acid production in airway epithelial cells". J. Biol. Chem. 279 (35): 36454–61. doi:10.1074/jbc.M404983200. PMID 15210697.
- Guzik TJ, Sadowski J, Kapelak B, et al. (2005). "Systemic regulation of vascular NAD(P)H oxidase activity and nox isoform expression in human arteries and veins". Arterioscler. Thromb. Vasc. Biol. 24 (9): 1614–20. doi:10.1161/01.ATV.0000139011.94634.9d. PMID 15256399.
- Ambasta RK, Kumar P, Griendling KK, et al. (2004). "Direct interaction of the novel Nox proteins with p22phox is required for the formation of a functionally active NADPH oxidase". J. Biol. Chem. 279 (44): 45935–41. doi:10.1074/jbc.M406486200. PMID 15322091.
- Park HS, Jung HY, Park EY, et al. (2004). "Cutting edge: direct interaction of TLR4 with NAD(P)H oxidase 4 isozyme is essential for lipopolysaccharide-induced production of reactive oxygen species and activation of NF-kappa B". J. Immunol. 173 (6): 3589–93. doi:10.4049/jimmunol.173.6.3589. PMID 15356101.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Jana A, Pahan K (2005). "Human immunodeficiency virus type 1 gp120 induces apoptosis in human primary neurons through redox-regulated activation of neutral sphingomyelinase". J. Neurosci. 24 (43): 9531–40. doi:10.1523/JNEUROSCI.3085-04.2004. PMC 1955476. PMID 15509740.
- Pedruzzi E, Guichard C, Ollivier V, et al. (2004). "NAD(P)H oxidase Nox-4 mediates 7-ketocholesterol-induced endoplasmic reticulum stress and apoptosis in human aortic smooth muscle cells". Mol. Cell. Biol. 24 (24): 10703–17. doi:10.1128/MCB.24.24.10703-10717.2004. PMC 533993. PMID 15572675.
- Djordjevic T, BelAiba RS, Bonello S, et al. (2005). "Human urotensin II is a novel activator of NADPH oxidase in human pulmonary artery smooth muscle cells". Arterioscler. Thromb. Vasc. Biol. 25 (3): 519–25. doi:10.1161/01.ATV.0000154279.98244.eb. PMID 15618545.
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