GSNOR

S-nitrosoglutathione reductase (GSNOR) is a cytoplasm localized enzyme which plays a key role in formaldehyde detoxification and is down regulated by wounding and activated by salicylic acid (SA). GSNOR reduces S-nitrosoglutathione (GSNO) to an unstable intermediate, S-hydroxylaminoglutathione, which then rearranges to form glutathione sulfonamide, or in the presence of GSH, forms oxidized glutathione (GSSG) and hydroxylamine. Through this catabolic process, GSNOR regulates the cellular concentrations of GSNO and plays a central role in regulating the levels of endogenous S-nitrosothiols and controlling protein S-nitrosylation-based signaling.

1208315-24-5
N6022
1208315-24-5

Background


An Overview of GSNOR

S-nitrosoglutathione reductase (GSNOR) is the main metabolic enzyme of S-nitrosoglutathione (GSNO) in vivo, which is a cytoplasmic localization enzyme. GSNOR can regulate the levels of nitric oxide (NO) and nitrosothiol (SNOs) in the cells through the GSNO pathway to protect the body from nitrosation stress. GSNOR participates in the regulation of NO signaling pathways in vivo by metabolizing GSNO, and has important physiological significance for the function of respiratory system, cardiovascular system and nervous system. Besides, GSNOR helps with formaldehyde detoxification. Damage caused by formaldehyde poisoning is downregulated by salicylic acid activation. GSNOR reduces GSNO to the unstable intermediate, S-hydroxyaminoglutathione, and then rearranges to form glutathione sulfonamide, or oxidized glutathione and hydroxylamine in the presence of GSH. In plants, GSNOR acts as a key enzyme that catalyzes the regulation of NO and its metabolite SNOs. GSNOR is involved in many physiological processes, such as plant growth, resistance to pathogens, heat tolerance, cell death and cadmium stress.

Inhibition of GSNOR

Inhibition of GSNOR enzymatic activity attenuates the inhibitory effect of the anti-inflammatory drug (Trichostatin A) on inflammatory factors. GSNOR is involved in the regulation of inflammatory factors by the anti-inflammatory drug Trichostatin A. Inhibition of inflammatory factor expression by up-regulating GSNOR may be a new way to inhibit inflammation.

GSNOR and Diseases

Recent studies have shown that elevated levels of protein nitrosylation in young sub-GSNOR knockout mice result in decreased muscle mass, decreased muscle fiber volume, and neuropathy, presenting a neuromuscular atrophy phenotype. Therefore, S-nitrosylation caused by GSNOR deficiency can cause neuromuscular dysfunction. GSNOR is a new important inflammatory regulatory molecule that may serve as a new potential target for the regulation of NO-mediated inflammation-related signaling pathways. Up-regulating GSNOR may be a new way to suppress inflammation. Excessive inflammatory responses are known to damage immune cells as well as normal tissues and lead to chronic inflammation and immune system related diseases such as endotoxemia, chronic arthritis, leukemia and cancer.

Reference:

Liu L., Hausladen A., Zeng M., Que L., Heitman J., Stamler J. S. (2001) A metabolic enzyme for S-nitrosothiol conserved from bacteria to humans. Nature, 410(6827): 490-494.