s-nitrosoglutathione (N30-201) / Vertex - LARVOL DELTA

[VIRTUAL] NitriCap Hemodialysis Catheter Insert to Prevent Catheter-Related Bloodstream Infection (KIDNEY WEEK 2020) - " Two cm long inserts using S-nitrosoglutathione (GSNO) as the NO donor and various other components were prepared and tested for their real-time NO release... This data strongly suggests that the NitriCap displays significant antimicrobial/anti-biofilm effects during in vitro and large animal in vivo studies, demonstrating that its implementation could minimize catheter related blood stream infections."

[VIRTUAL] Nitric Oxide (NO) Based Urinary Catheter Balloon Inflation Solution to Prevent Urinary Tract Infection (KIDNEY WEEK 2020) - " Our innovative approach to prevent CAUTI involves employing a balloon inflation fluid using novel NO secreting materials based on using S-nitrosothiol type NO donors like S-nitrosoglutathione (GSNO) within the balloon of urinary catheters that slowly releases NO over a period of up to one week... These data suggest that NO-based urinary catheter balloon fluid results in significant anti-microbial effects in our in vitro model of CAUTI."

Infectious Disease • Nephrology

Overexpression of SlGSNOR impairs in vitro shoot proliferation and developmental architecture in tomato but confers enhanced disease resistance. (PubMed, J Plant Physiol) - "S-NITROSOGLUTATHIONE REDUCTASE (GSNOR) governs NO bioavailability by the breakdown of S-nitrosoglutathione (GSNO), fine-tunes NO signalling and controls total cellular S-nitrosylated proteins...Furthermore, SlGSNOR O.E plants exhibited altered leaf arrangement, fruit shape and modified locules number in tomato fruit. These findings give a novel insight into a multifaceted regulatory role of SlGSNOR in tomato plant development, reproduction and response to pathogens."

Journal • Preclinical • Developmental Disorders

[VIRTUAL] Cystic Fibrosis Airway Cells Are Less Susceptible to SARS-CoV-2 Infection and Have Altered pH Regulatory Protein Expression (ATS 2021) - "Levels of pH regulatory proteins NHERF1, LDHd, LDHb, LDHa, glutaminase, S-nitrosoglutathione reductase (GSNOR), DUOX1, CCNO, carbonic anhydrase 2 (CA2), carbonic anhydrase 12 (CA12), and ATP12a S-were measured in cell lysates from the same CF and non-CF HAECs by JESS automated western blot (ProteinSimple, San Jose, CA, USA)... CF HAECs are less susceptible to SARS-CoV-2 viral infection that non-CF HAECs. This may be due to the increased intracellular pH in CF HAECs compared to non-CF HAECs. Since carbonic anhydrases produce bicarbonate ions, CA2 and CA12 upregulation may contribute to increased intracellular pH in CF along with decreased bicarbonate extrusion due to CFTR function loss."

Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • LDHA • LDHB

Vacuolar H+-ATPase and Na+/K+-ATPase energize Na+ uptake mechanisms in the nuchal organ of the hyperregulating freshwater crustacean Daphnia magna. (PubMed, J Exp Biol) - "Na+ influx across the nuchal organ was inhibited both by inhibitors of the Na+/K+-ATPase (ouabain, bufalin) and by inhibitors of the vacuolar H+-ATPase (bafilomycin, N-ethylmaleimde, 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole, KM91104, S-nitrosoglutathione). Na+ influx was unaffected by the epithelial Na+ channel blocker benzamil, but was sensitive to ethylisopropyl amiloride and elevated external ammonium concentrations, consistent with roles for Na+/H+ and Na+/NH4+ exchangers in the apical membrane but not Na+ channels. Transport across the basolateral membrane into the hemolymph is proposed to involve the Na+/K+-ATPase and a thiazide-sensitive Na+:Cl- cotransporter. Keywords: Daphnia magna, Na+/K+-ATPase, V-ATPase, Iionoregulation, Nnuchal organ."

Journal

NCX-4040, a Unique Nitric Oxide Donor, Induces Reversal of Drug-Resistance in Both ABCB1- and ABCG2-Expressing Multidrug Human Cancer Cells. (PubMed, Cancers (Basel)) - "In this study, we have used cytotoxicity and molecular docking studies to show that NCX4040, a nitric oxide donor related to aspirin, inhibited the functions of ATPase which resulted in significant reversal of resistance to both adriamycin and topotecan in P-gp- and BCRP-expressing human cancer cell lines, respectively. We also used several other cytotoxic nitric oxide donors, e.g., molsidomine and S-nitroso glutathione; however, both P-gp- and BCRP-expressing cells were found to be highly resistant to these NO-donors. Molecular docking studies showed that NCX4040 binds to the nucleotide binding domains of the ATPase and interferes with further binding of ATP, resulting in decreased activities of these transporters. Our results are extremely promising and suggest that nitric oxide and other reactive species delivered to drug resistant tumor cells by well-designed nitric oxide donors could be useful in sensitizing anticancer drugs in multidrug resistant tumors expressing..."

Journal • Breast Cancer • Oncology • Solid Tumor • ABCB1 • ABCG2

Redox sensor QSOX1 regulates plant immunity by targeting GSNOR to modulate ROS generation. (PubMed, Mol Plant) - "QSOX1 both senses and regulates ROS levels through interaction with and redox-mediated regulation of S-nitrosoglutathione reductase that, consistent with previous findings, influences reactive nitrogen-mediated regulation of ROS generation. Collectively, our data indicate that QSOX1 is a redox sensor that negatively regulates plant immunity by linking reactive oxygen- and reactive nitrogen-signaling to limit ROS production."

Journal • QSOX1

Pharmacological Inhibition of S-Nitrosoglutathione Reductase Reduces Cardiac Damage Induced by Ischemia-Reperfusion. (PubMed, Antioxidants (Basel)) - "These results were associated with increasing protein S-nitrosylation, specifically of the mitochondrial complexes III and V. The pharmacological inhibition of GSNOR showed a concentration-dependent cardioprotective effect, being observed in functional parameters and myocardial damage, which was maximal at 1 µmol/L, associated with increased S-nitrosylation of mitochondrial proteins. These data suggest that GSNOR is an interesting pharmacological target for cardiac reperfusion injury."

Journal • Cardiovascular • Coronary Artery Disease • Myocardial Ischemia • Reperfusion Injury

Root NRT, NiR, AMT, GS, GOGAT and GDH expression levels reveal NO and ABA mediated drought tolerance in Brassica juncea L. (PubMed, Sci Rep) - "Further, increases in activities of L-arginine dependent NOS-like enzyme and S-nitrosoglutathione reductase were observed under nitrate agonist treatments. This indicates that the balanced endogenous change in NO and ABA levels together during synthesis and degradation of NO mitigated the oxidative stress in Indian mustard seedlings. Overall, our results reveal that NO independently or together with ABA may contribute to improved crop growth and productivity under drought stress."

Biomarker • Journal

Au Catalyzing Control Release NO in vivo and Tumor Growth-Inhibiting Effect in Chemo-Photothermal Combination Therapy. (PubMed, Int J Nanomedicine) - "In vivo, 11.7 μg Au in the tumor tissue was found to catalyze S-nitrosoglutathione continuously, and 54 μM NO was checked out in the urine. The high concentration of NO was found to increase the apoptotic rate and to reduce tumor proliferation. In the chemo-photothermal combination therapy, the tumor inhibition rate was increased up to 94.3%, and Au's contribution from catalyzing NO release NO was 8.17%."

Combination therapy • Journal • Preclinical • Oncology

Protein S-nitrosylation regulates proteostasis and viability of hematopoietic stem cell during regeneration. (PubMed, Cell Rep) - "S-nitrosoglutathione reductase (GSNOR)-deleted HSCs exhibit a reduced reconstitution capacity and loss of self-renewal after chemotherapeutic injury, which is resolved by inhibition of NO synthesis...Treatment of taurocholic acid (TCA), a chemical chaperone, rescues the regeneration defect of Gsnor HSCs after 5-fluorouracil (5-FU) treatment. Deletion of C/EBP homologous protein (Chop) restores the reconstitution capacity of Gsnor HSCs. These findings establish a link between S-nitrosylation and protein aggregation in HSC in the context of blood regeneration."

Journal

Bronchopulmonary Dysplasia and Pulmonary Hypertension: The Role of Smooth Muscle adh5. (PubMed, Am J Respir Cell Mol Biol) - "In our BPD model, we have investigated the metabolism of the bronchodilator and pulmonary vasodilator S-nitrosoglutathione (GSNO)...Expression in the pulmonary vasculature is relevant to the pathophysiology of BPD-associated pulmonary hypertension. GSNO-mimetic agents or GSNO reductase inhibitors, both of which are currently in clinical trials for other conditions, could be considered for further study in BPD."

Journal • Bronchopulmonary Dysplasia • Hypertension • Pulmonary Arterial Hypertension • Respiratory Diseases

Induction of S-nitrosoglutathione reductase protects root growth from ammonium toxicity by regulating potassium homeostasis in Arabidopsis and rice. (PubMed, J Exp Bot) - "GSNOR overexpression enhanced vtc1-1 root tolerance to NH4 +. The findings suggest that induction of GSNOR increases NH4 + tolerance in Arabidopsis roots by counteracting NO-mediated suppression of tissue K +, which depends on VTC1 function."

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[VIRTUAL] Nitric Oxide-Therapy but Not Remote Ischemic Conditioning is Cerebroprotective in Stroke - A Study in Mouse Model of Endothelial Dysfunction and Hypertension (ISC 2021) - P=N/A | "As needed, mice were treated with RIC, s-nitrosoglutathione (GSNO) reductase inhibitor (GRI; 5 mg/kg nebulized once daily for 2-wks), GSNO (100-ug/kg; nebulized once daily at 2h post-TES), and/or intravenous thrombolysis (IVT; 10mg/kg at 4h post-TES)... NO-therapies but not RIC is effective in hypertensive stroke. RIC- and NO- therapies need further validation in comorbid stroke before embarking on the clinical trial."

Preclinical • Cardiovascular • Hypertension • Ischemic stroke

Shank3 mutation in a mouse model of autism leads to changes in the S-nitroso-proteome and affects key proteins involved in vesicle release and synaptic function. (PubMed, Mol Psychiatry) - "S-nitrosoglutathione concentrations were higher in mutant mice compared to WT. This is the first study on NO-related molecular changes and SNO-signaling in the brain of an ASD mouse model that allows the characterization and identification of key proteins, cellular pathways, and neurobiological mechanisms that might be affected in ASD."

Journal • Preclinical • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Genetic Disorders • Mental Retardation • Psychiatry

Cardiovascular "Patterns" of HS and SSNO-Mix Evaluated from 35 Rat Hemodynamic Parameters. (PubMed, Biomolecules) - "Since HS, NO donor S-nitrosoglutathione (GSNO) and their HS/GSNO products (SSNO-mix) have numerous biological actions, we aimed to compare their effects on APW and to find characteristic "patterns" of their actions...Effect of SSNO-mix (≤32 nmol kg) on blood pressure in the presence or absence of a nitric oxide synthase inhibitor (L-NAME) was minor in comparison to GSNO, suggesting that the formation of SSNO-mix in blood diminished the hemodynamic effect of NO. The observed time-dependent changes of 35 HPs, their cross-relationships and non-hysteresis/hysteresis profiles may serve as "patterns" for the conditions of a transient decrease/increase of blood pressure caused by HS."

Journal • Anesthesia • Cardiovascular

Dual Roles of GSNOR1 in Cell Death and Immunity in Tetraploid Nicotiana tabacum. (PubMed, Front Plant Sci) - "S-nitrosoglutathione reductase 1 (GSNOR1) is the key enzyme that regulates cellular homeostasis of S-nitrosylation...tomato DC3000 was significantly reduced (p < 0.01) in the NtGSNOR1a/1b knockout lines. In summary, our results indicate that NtGSNOR1 functions as both positive and negative regulator of cell death under different conditions and displays distinct effects on resistance against viral and bacterial pathogens."

Journal • CASP9

Pretreatment with S-Nitrosoglutathione Attenuates Septic Acute Kidney Injury in Rats by Inhibiting Inflammation, Oxidation, and Apoptosis. (PubMed, Biomed Res Int) - "Furthermore, pretreatment with SNG significantly reduced the apoptotic rate of KTEC and decreased the levels of caspase-3 and Bax mRNA, but increased the level of Bcl-2 mRNA. Pretreatment with SNG has a protective effect on AKI in septic rats, and the specific mechanisms are related to inhibition of inflammation, oxidation, and apoptosis."

IO biomarker • Journal • Acute Kidney Injury • Immunology • Infectious Disease • Inflammation • Nephrology • Renal Disease • Septic Shock • BCL2 • CASP3 • IL1B • KIM1 • LCN2 • TNFA

Nuclear localization of endothelial nitric oxide synthase and nitric oxide production attenuates aphidicolin-induced endothelial cell death. (PubMed, Nitric Oxide) - "However, exogenous NO donors including S-nitroso-L-glutathione (GSNO) or diethylenetriamine NONOate (DETA NO) had no effect on aphidicolin-decreased BAEC viability and aggravated BAEC viability at higher doses...Finally, expression of N-myristoyltransferase 2 (NMT2) but not NMT1 significantly decreased in aphidicolin-treated BAECs. Taken together, our results suggest that aphidicolin attenuates BAEC death in part by increasing nuclear eNOS localization and NO production."

Journal • NOS3

GSNOR and ALDH2 alleviate traumatic spinal cord injury. (PubMed, Brain Res) - "Traumatic spinal cord injury (SCI) enhances the activity of S-nitrosoglutathione reductase (GSNOR) and inhibits the mitochondrial aldehyde dehydrogenase 2 (ALDH2) activity, resulting in prolonged and sustained pain and functional deficits. Combining the specific inhibitor of GSNOR (N6022) with the selective activator of ALDH2 (Alda-1) provides greater protection to the neurovascular unit and confers greater functional recovery. The study is novel, and the combination therapy (N6022+Alda-1) possesses translational potential."

Journal • CNS Disorders • Complement-mediated Rare Disorders • Orthopedics • Pain • ALDH2

Comparative Study of Several Fe Deficiency Responses in the Arabidopsis thaliana Ethylene Insensitive Mutants ein2-1 and ein2-5. (PubMed, Plants (Basel)) - "The results obtained show that both mutants do not induce subapical root hairs either under Fe deficiency or upon treatments with the ET precursor 1-aminocyclopropane-1-carboxylate (ACC) and the NO donor S-nitrosoglutathione (GSNO)...All these results clearly support the participation of ET and NO, through EIN2, in the regulation of subapical root hairs and Fe acquisition genes. The results will be discussed, taking into account the role of both ET and NO in the regulation of Fe deficiency responses."

Journal

Protein S-nitrosation differentially modulates tomato responses to infection by hemi-biotrophic oomycetes of Phytophthora spp. (PubMed, Hortic Res) - "S-nitrosoglutathione is regarded as the most abundant low-molecular-weight S-nitrosothiol in plants, where its intracellular concentrations are modulated by S-nitrosoglutathione reductase...Ascorbate peroxidase S-nitrosation was observed in both genotypes in parallel to increased enzyme activity and protein level during P. infestans pathogenesis, namely in the susceptible genotype. These results show important regulatory functions of protein S-nitrosation in concerting molecular mechanisms of plant resistance to hemibiotrophic pathogens."

Journal

BH4 Increases nNOS Activity and Preserves Left Ventricular Function in Diabetes. (PubMed, Circ Res) - "In HEK cells, S-nitrosoglutathione led to a PKG-dependent increase in plasmalemmal density of the insulin-independent glucose transporter, GLUT-1... We uncovered a novel mechanism whereby myocardial BH4 prevents and reverses LV diastolic and systolic dysfunction associated with diabetes via a nNOS-mediated increase in non-insulin dependent myocardial glucose uptake and utilization. These findings highlight the potential of GCH1/BH4-based therapeutics in human diabetic cardiomyopathy."

Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • NOS1 • SLC2A1

S-nitrosoglutathione Reductase-Mediated nitric oxide affects axillary buds outgrowth of solanum lycopersicum L. by regulating auxin and cytokinin signaling. (PubMed, Plant Cell Physiol) - "NR-mediated NO reduced the GSNOR activity through S-nitrosylation of Cys-10, then induced a further NO burst, which played the above roles to promote axillary buds outgrowth. Together, GSNOR-mediated NO played important roles in controlling axillary buds outgrowth via altering the homeostasis and signaling of auxin and cytokinin in tomato plants."

Journal

Loss of function of the chloroplast membrane K/H antiporters AtKEA1 and AtKEA2 alters the ROS and NO metabolism but promotes drought stress resilience. (PubMed, Plant Physiol Biochem) - "Furthermore, the S-nitrosoglutathione reductase (GSNOR) protein expression and activity were downregulated in kea1kea2 mutants, whereas the tyrosine nitrated protein profile, analyzed by immunoblot, was unaffected but the relative expression of each immunoreactive band changed...Data suggest that the chloroplast osmotic balance and integrity maintained by AtKEA1 and AtKEA2 are necessary to keep the balance of ROS/RNS metabolism. Moreover, these data open new questions about how endogenous NO generation might be affected by the K/H transport located in the chloroplasts."

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