Nitric oxide synthase 2 (inducible) explained

Nitric oxide synthase, inducible is an enzyme which is encoded by the NOS2 gene in humans and mice.^[1]

Genetics

Three related pseudogenes are located within the Smith-Magenis syndrome region on chromosome 17. Alternative splicing of this gene results in two transcript variants encoding different isoforms.^[2]

Location

Nitric oxide synthase is expressed in epithelial cells of the liver, lung and bone marrow. It is inducible by a combination of lipopolysaccharide and certain cytokines.

Function

Nitric oxide is a reactive free radical mediating in neurotransmission, antimicrobial and antitumoral activities.In mice, the function of Nos2 in immunity against a number of viruses, bacteria, fungi, and parasites has been well characterized, whereas in humans the role of NOS2 has remained elusive and controversial.^[3] Nos2 is important for protective immunity against CMV.

Caveolin 1 has been shown to interact with Nitric oxide synthase 2A.^[4] and Rac2.^[5]

Deficiency

Autosomal recessive NOS2 deficiency has been described in mice. They lack the gene encoding nitric oxide synthase 2 (Nos2) and are susceptible to murine CMV infection.^[6]

In February 2020, the same autosomal recessive, complete NOS2 deficiency was described in a human. A 51-year-old previously healthy person died after 29 months of progressive CMV infection due to respiratory failure secondary to CMV pneumonitis, CMV encephalitis, and hemophagocytic lymphohistiocytosis. Whole-exome sequencing on genomic DNA from his blood showed he had homozygous variants in five genes. The only loss-of-function variant was a homozygous frameshift mutation in nitric oxide synthase 2. This condition is extremely rare, occurring in fewer than 1 per million persons.^[7]

Notes and References

1. Geller DA, Lowenstein CJ, Shapiro RA, Nussler AK, Di Silvio M, Wang SC, Nakayama DK, Simmons RL, Snyder SH, Billiar TR . Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes . Proc Natl Acad Sci USA . 90 . 8 . 3491–5 . May 1993 . 7682706 . 46326 . 10.1073/pnas.90.8.3491 . 1993PNAS...90.3491G . free .
2. Web site: Entrez Gene: NOS2A nitric oxide synthase 2A (inducible, hepatocytes).
3. Nathan . C. . 2006-06-30 . Role of iNOS in Human Host Defense . Science . en . 312 . 5782 . 1874b–1875b . 10.1126/science.312.5782.1874b . 16809512 . 37395425 . 0036-8075.
4. Felley-Bosco E, Bender FC, Courjault-Gautier F, Bron C, Quest AF . Caveolin-1 down-regulates inducible nitric oxide synthase via the proteasome pathway in human colon carcinoma cells . . 97 . 26 . 14334–9 . December 2000 . 11114180 . 18919 . 10.1073/pnas.250406797 . 2000PNAS...9714334F . free .
5. Kuncewicz T, Balakrishnan P, Snuggs MB, Kone BC . Specific association of nitric oxide synthase-2 with Rac isoforms in activated murine macrophages . Am. J. Physiol. Renal Physiol. . 281 . 2 . F326–36 . August 2001 . 10.1152/ajprenal.2001.281.2.F326 . 11457725 . 15719851 .
6. Noda . Satoshi . Tanaka . Kazuo . Sawamura . Sada-aki . Sasaki . Masafumi . Matsumoto . Takako . Mikami . Katsunaka . Aiba . Yuji . Hasegawa . Hideaki . Kawabe . Noboru . Koga . Yasuhiro . 2001-03-01 . Role of Nitric Oxide Synthase Type 2 in Acute Infection with Murine Cytomegalovirus . The Journal of Immunology . en . 166 . 5 . 3533–3541 . 10.4049/jimmunol.166.5.3533 . 11207313 . 0022-1767. free .
7. Drutman . Scott B. . Mansouri . Davood . Mahdaviani . Seyed Alireza . Neehus . Anna-Lena . Hum . David . Bryk . Ruslana . Hernandez . Nicholas . Belkaya . Serkan . Rapaport . Franck . Bigio . Benedetta . Fisch . Robert . 2020-01-30 . Fatal Cytomegalovirus Infection in an Adult with Inherited NOS2 Deficiency . New England Journal of Medicine . en . 382 . 5 . 437–445 . 10.1056/NEJMoa1910640 . 31995689 . 0028-4793. 7063989 .