(GSNOR is also referred to as GS-FDH, FDH, and ADH3)
1955:
Strittmatter and Ball (J Biol Chem,, 213:445) report isolation from beef and chicken liver of a specific diphosphopyridine nucleotide (DPN) dependent formaldehyde dehydrogenase requiring reduced glutathione as a cofactor.
1974:
Uotila and Koiunsalo (J Biol Chem 249:7653) report similar finding from human liver homogenates, and comment, “The Physiologic significance of formaldehyde dehydrogenase is unclear at the present time.”
1980:
Kuwad et al (J Biochem <Tokyo> 88:859) first implicate FDH in the metabolism of nitroso compounds, coining the term “nitroso reductases;” however, they view it as nonspecific function of hepatocytes.
1984:
Khan et al (Cytogenet Cell Genet 38:112) assign formaldehyde dehydrogenase (FDH) to human chromosome 4.
1989:
Koivusalo and Uotila (FEBS Lett 257:105) publish that FDH is a widely occurring enzyme in multiple species and that rat FDH and Class III mammalian alcohol dehydrogenase are identical enzymes.
1990:
Holmquist et al (J Protein Chem 10:69) expand Kolvusalo et als’ observation to show Human Class III ADH is same as FDH.
1996:
Martinez et al (Eur J Biochem 241:849) report that plants, and “all life forms” share class III alcohol dehydrogenase.
1997:
Fliegmann and Sandermann (Plant Mol Biol 34:843) first report FDH as important plant detoxifying enzyme and set the stage for future reports of FDH in plant host-defense.
1998:
Jensen et al (Biochem J 15:331) first publish that GSNO is “an exceptionally active substrate” for FDH.
1998:
Gaston et al (Lancet 351:1317) report that GSNO levels are decreased in the airway lining fluid of children with near-fatal asthma, adding asthma to the other known associations of GSNO with cardiovascular function, blood clotting, cellular apoptosis, ion channel deactivations, and cellular inflammation.
2001:
(Hoog et al (J Biomed Sci 8:71) postulate that entire ADH system may be seen as a general detoxifying system for alcohol and aldehydes without generating toxic radicals in contrast to the cytochrom3 P450 system.)
2001:
Liu et al (Nature 410:490) present evidence in bacteria, yeast, and knock-out mice that GS-FDH is the primary means for degradation of GSNO, independent of other redox cofactors,, and is important for regulating SNO homeostasis.
2003:
Haqqani et al (Nitric Oxide 9:172) publish cellular studies showing inhibition of FDH activity leads to increased intracellular protein S-nitrosation.
2004:
Using GSNOR -/- mice Liu et al (Celll 116:617) report nitrosative stress induced in such animals by endotoxiin or bacterial challenge.
2005:
Que et al (Science 308:1616) publish productive effect of GSNOR -/- in a murine model of asthma.
2007:
Haqqani et al (J Proteome Res 6:226) find that GSNOR is one of only 15 protein markers increased in the inflammatory ischemic insult in experimental brain ischemia.
2007:
Wu et al (J Allergy Clin Immunol 120:322) publish findings that genetic variations in GSNOR are associated with childhood asthma.
2008:
Thompson and Grafstom (J Toxicol Environ Health A 71:244) hypothesize that ADH3-associated deregulation of GSNO turnover influenced by formaldehyde might exacerbate asthma and induce bronchoconstricution. (in 2090, Thompson et al continue to make this argument <Drug Metab Dispos 37:1565>).
2009:
Stabb et al (Chem Biol Interact 178:29) also argue that ADH3-medicated GSNO depletion might be important in asthma and under conditions of oxidative stress, GSNO reduction can lead to the formation of glutathione sulfinamide and its hydrolyis product glutathione sulfinic acid–both potent inhibitors of glutathione transferase activity.
2009:
Lima et al (Proc Natl Acad Sci USA 106: 6297) claim that experimental myocardial injury is prevented in GSNOR -/- mice.
2009:
Studying the bronchoalveolar lavage (BAL) of asthmatic patients, Que et al (Jm J Respir Crit Care Med 180:226) report GSNOR activity was increased and SNO levels decreased in asthmatics as compared to controls. Levels correlated inversely with the provocative concentration of methacholine causing a 20% decrease in FEV1.
2009:
Moore et al (Pediatr Pulmonol 44:659) expand the genetic argument for importance of GSNOR by showing a genotype variation in GSNOR is associated with a decreased response to asthma treatment (albuterol) in African American children presenting with severe asthma.
2010:
Choudhry et al (Pharmacogeneti Genomics 20:351) study GSNOR genetics in Latino individuals finding several GSNOR SNPs and a haplotype in the 3UTR significantly associates with increased risk for asthma and lower bronchocdilator responsiveness. The GSNOR risk haplotype affected expression of GSNOR mRNA and protein suggesting a gain of GSNOR function. They also found a genetic relationship between GSNOR and beta2AR gene variants and response to albuterol.
2010:
Wu et al (J Pharmacol Science 113:32) report increased GSNOR activity in experimental pulmonary hypertension.
2010:
Sun et al (Gordon Research Conference) present first discovery and development of novel, high potency small molecule inhibitors of GSNOR. Of interest, in contrast to GSNOR -/- mice, such molecules show pronounced anti-inflammatory activity in experimental asthma and other disease models of inflammation.
2010:
N30 Pharma begins human testing of N6022, a proprietary GSNOR inhibitor.