Protein-coding gene in the species Homo sapiens
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] [ 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
^ a b c GRCh38: Ensembl release 89: ENSG00000086991 – Ensembl , May 2017^ a b c 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 .^ a b "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 .
