• Bulletin of the Korean Chemical Society
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• v.26 no.6
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• pp.995-997
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• 2005

• Biomolecules & Therapeutics
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• v.26 no.6
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• pp.533-538
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• 2018

Nitric oxide (NO) mediates various physiological and pathological processes, including cell proliferation, differentiation, and inflammation. Protein S-nitrosylation (SNO), a NO-mediated reversible protein modification, leads to changes in the activity and function of target proteins. Recent findings on protein-protein transnitrosylation reactions (transfer of an NO group from one protein to another) have unveiled the mechanism of NO modulation of specific signaling pathways. The intracellular level of S-nitrosoglutathione (GSNO), a major reactive NO species, is controlled by GSNO reductase (GSNOR), a major regulator of NO/SNO signaling. Increasing number of GSNOR-related studies have shown the important role that denitrosylation plays in cellular NO/SNO homeostasis and human pathophysiology. This review introduces recent evidence of GSNO-mediated NO/SNO signaling depending on GSNOR expression or activity. In addition, the applicability of GSNOR as a target for drug therapy will be discussed in this review.

• Journal of Microbiology and Biotechnology
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• v.26 no.5
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• pp.928-937
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• 2016

S-Nitrosoglutathione reductase (GSNOR) metabolizes S-nitrosoglutathione (GSNO) and has been shown to play important roles in regulating cellular signaling and formulating host defense by modulating intracellular nitric oxide levels. The enzyme has been found in bacterial, yeast, mushroom, plant, and mammalian cells. However, to date, there is still no evidence of its occurrence in filamentous fungi. In this study, we cloned and investigated a GSNOR-like enzyme from the filamentous fungus Aspergillus nidulans. The enzyme occurred in native form as a homodimer and exhibited low thermal stability. GSNO was an ideal substrate for the enzyme. The apparent K_m and k_cat values were 0.55 mM and 34,100 min^-1, respectively. Substrate binding sites and catalytic center amino acid residues based on those from known GSNORs were conserved in this enzyme, and the corresponding roles were verified using site-directed mutagenesis. Therefore, we demonstrated the presence of GSNOR in a filamentous fungus for the first time.

• Archives of Pharmacal Research
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• v.16 no.1
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• pp.1-5
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• 1993

The reaction of sulfhydryl groups in human serum ablumin with bacteriostatic and hypotensive notrosating agents such as sodium nitorprusside and sodium nitrite has been examined. The low reactivity of sodium nitroprusside to sulfhydral groups in albumin has been observed and the sterical inaccessilibility of the agent site which sulfhydryl group resides was implicated. The reaction of sodium nitrite with albumin was highly influenced by pH and little reactivity was observed at physiological pH. On the other hand, the reaction between albumin and S-nitrosoglutatione, an intermediate induced from the reaction of glutathione and nitrosating agents, resulted in the rapid decrease of free sulfhydryl groups in albumin. S-Nitrosylation of the sulfhydryl group by S-nitrosoglutathione and the subsequent production of mixed disulfide is the probable route of modification. In the physiological system, S-nitroso-glutathione may act as an active intermediate in expressing reacivity of nitrosating agents to sulfhydryl groups in albumin.

• BMB Reports
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• v.44 no.12
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• pp.782-786
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• 2011

Aberrant GAPDH expression following S-nitrosoglutathione (GSNO) treatment was compared in HepG2 cells, which express functional p53, and Hep3B cells, which lack functional p53. The results of Western blotting and fluorescent immunocytochemistry revealed that nuclear translocation and accumulation of GAPDH occur in both HepG2 and Hep3B cells. This finding suggests that p53 may not be necessary for the GSNO-induced translocation of GAPDH to the nucleus during apoptotic cell death in hepatoma cells.

• Annals of Clinical Neurophysiology
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• v.8 no.1
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• pp.63-70
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• 2006

Background: Testosterone is reported to have neuroprotective effect in various neurological diseases. Recently, the mechanism involved in nitric oxide (NO)-mediated motor neuron death is under extensive investigation. The Cu/Zn-superoxide dismutase (SOD1) mutations has been implicated in selective motor neuron death of amyotrophic lateral sclerosis (ALS) and it is said to play an important role in NO-mediated motor neuron death. However, neuroprotective effect of testosterone on motor neuron exposed to NO has rarely been studied. Methods: Motor neuron-neuroblastoma hybrid cells expressing wild-type or mutant (G93A or A4V) SOD gene were treated with $200{\mu}M$ S-nitrosoglutathione. After 24 hr, cell viability was measured by MTT assay. To see the neuroprotective effect of testosterone, pretreatment with 1 nM testosterone was done 1 hr before S-nitroglutathione treatment. To study the mechanism of protective effect, $20{\mu}M$ flutamide (androgen receptor antagonist) was also pretreated with testosterone 1 hr before S-nitroglutathione treatment. Results: S-nitrosoglutathione showed significant neurotoxic effect in all three cell lines. Percentage of cell death was somewhat different in each cell line. 1 nM testosterone showed neuroprotective effect in G93A and wild-type cell line. In A4V cell line, testosterone did not showed neuroprotective effect. The neuroprotective effect of testosterone was reversed by $20{\mu}M$ flutamide. Conclusions: These results indicate that testosterone induces neuroprotection in NO-mediated motor neuron death directly through the androgen receptor. This neuroprotective effect of testosterone varies according to the types of SOD1 gene mutation. These data suggest that testosterone may be of therapeutic value against ALS.

• Journal of Animal Reproduction and Biotechnology
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• v.35 no.1
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• pp.102-111
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• 2020

Nitric oxide (NO)-induced protein S-nitrosylation triggers mitochondrial dysfunction and was related to cell senescence. However, the exact mechanism of these damages is not clear. In the present study, to investigate the relationship between in vitro aging and NO-induced protein S-nitrosylation, oocytes were treated with sodium nitroprusside dihydrate (SNP), and the resultant S-nitrosylated proteins were detected through biotin-switch assay. The results showed that levels of protein S-nitroso thiols (SNO)s and expression of S-nitrosoglutathione reductase (GSNOR) increased, while activity and function of mitochondria were impaired during oocyte aging. Addition of SNP, a NO donor, to the oocyte culture led to accelerated oocyte aging, increased mitochondrial dysfunction and damage, apoptosis, ATP deficiency, and enhanced ROS production. These results suggested that the increased NO signal during oocyte aging in vitro, accelerated oocyte degradation due to increased protein S-nitrosylation, and ROS-related redox signaling.

• BMB Reports
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• v.42 no.7
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• pp.456-461
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• 2009

Proteomic analyses of differentially expressed proteins in rat retinal ganglion cells (RGC-5) following S-nitrosoglutathione (GSNO), an NO donor, treatment were conducted. Of the approximately 314 protein spots that were detected, 19 were differentially expressed in response to treatment with GSNO. Of these, 14 proteins were up-regulated and 5 were down- regulated. Notably, an increase in GAPDH expression following GSNO treatment was detected in RGC-5 cells through Western blotting as well as proteomics. The increased GAPDH expression in response to GSNO treatment was accompanied by an increase in Herc6 protein, an E3 ubiquitin ligase. Moreover, GSNO treatment resulted in the translocation of GADPH from the cytosol to the nucleus and its subsequent accumulation. These results suggest that NO stress-induced apoptosis may be associated with the nuclear translocation and accumulation of GAPDH in RGC-5 cells.

• Proceedings of the Korean Society of Crop Science Conference
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• 2022.10a
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• pp.159-159
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• 2022

Nitric oxide (NO) is a versatile signaling molecule, which is not only involved in plant growth and development but also regulates biological processes in response to biotic and abiotic stresses. Exogenous application of NO regulates the endogenous level of nitric oxide in response to stress conditions and therefore, NO donors are frequently used for stress alleviation. However, NO has very short half-life along with high reactivity. Therefore, conventional NO donors are often disadvantageous due to the relative instability of NO. On the contrary, development of NO releasing nanoparticles is a potential technique for enhancing the availability of NO in plants. Therefore, our aim was to synthesize such potential NO releasing nanoparticles which may be useful for application in agriculture. We have prepared Chitosan encapsulated S-nitrosoglutathione nanoparticles (GSNONP) and tried it with different concentrations for basic research in Arabidopsis thaliana. Our results suggest that lower concentration of this nanoparticle is highly effective for better growth of plants whereas higher concentration produces toxicity that leads to plant death. We observed better growth of Arabidopsis thaliana at 1µM concentration of the GSNONP compared to free GSNO.

• Proceedings of the Korean Society of Crop Science Conference
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• 2023.04a
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• pp.105-105
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• 2023

Heavy metals, including lead (Pb) toxicity, are increasing in soil and are considered toxic in small amounts. Pb contamination is mainly caused by industrialization - smelting, mining. Agricultural practices - sewage sludge, pests and urban practices - lead paint. It can seriously damage and threaten crop growth. Pb can adversely affect plant growth and development by affecting the photosystem, cell membrane integrity, and excessive production of reactive oxygen species (ROS) such as hydrogen peroxide (H₂O₂)andsuperoxide(O₂.-). NO is produced via enzymatic and non-enzymatic antioxidants to scavenge ROS and lipid peroxidation substrates in terms of protecting cells from oxidative damage. Thus, NO improves ion homeostasis and confers resistance to metal stress. Our results here suggest that exogenous NO may aid in better growth under lead stress. These enhancements may be aided by NO's ability in sensing, signaling and stress tolerance in plants under heavy metal stress in combination with lead stress. Our results show that GSNO has a positive effect on soybean seedling growth in response to axillary pressure and that NO supplementation helps to reduce chlorophyll maturation and relative water content in leaves and roots following strong burst under lead stress. GSNO supplementation (200 µM and 100 µM) reduced compaction and approximated oxidative damage of MDA, proline and H₂O₂. Under plant tension, a distorted appearance was found in the relief of oxidative damage by ROS scavenging by GSNO application. In summary, modulation of these NO, PCS and prolongation of metal past reversing GSNO application confirms the detoxification of ROS induced by toxic metal rates in soybean. In summary, these NO, PCS and metal traditionally sustained rates of reverse GSNO application confirm the detoxification of ROS induced by toxic metal rates in soybean.