ArticlePloS one2010
Diazeniumdiolate mediated nitrosative stress alters nitric oxide homeostasis through intracellular calcium and S-glutathionylation of nitric oxide synthetase.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Paradoxical Roles of Antioxidant Enzymes: Basic Mechanisms and Health Implications.Physiological reviews · 2016Review
- Glutathionylation mediates angiotensin II-induced eNOS uncoupling, amplifying NADPH oxidase-dependent endothelial dysfunction.Journal of the American Heart Association · 2014Article
- Pleiotropic functions of glutathione S-transferase P.Advances in cancer research · 2014Article
- Redox modulation of endothelial nitric oxide synthase by glutaredoxin-1 through reversible oxidative post-translational modification.Biochemistry · 2013Article
- Causes and consequences of cysteine S-glutathionylation.The Journal of biological chemistry · 2013Review
- Sulfiredoxin redox-sensitive interaction with S100A4 and non-muscle myosin IIA regulates cancer cell motility.Biochemistry · 2012Article
- Regulation of mitochondrial processes by protein S-nitrosylation.Biochimica et biophysica acta · 2012Review
- Protein S-glutathiolation: redox-sensitive regulation of protein function.Journal of molecular and cellular cardiology · 2012Review
- S-Glutathionylation of Protein Disulfide Isomerase Regulates Estrogen Receptor α Stability and Function.International journal of cell biology · 2012Article
- Alteration of ceramide synthase 6/C16-ceramide induces activating transcription factor 6-mediated endoplasmic reticulum (ER) stress and apoptosis via perturbation of cellular Ca2+ and ER/Golgi membrane network.The Journal of biological chemistry · 2011Article
- The role of glutathione S-transferase P in signaling pathways and S-glutathionylation in cancer.Free radical biology & medicine · 2011Review
- S-glutathionylation: from molecular mechanisms to health outcomes.Antioxidants & redox signaling · 2011Review
- S-glutathionylation: a redox-sensitive switch participating in nitroso-redox balance.Circulation research · 2011Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPABA/NO is a diazeniumdiolate that acts as a direct nitrogen monoxide (NO) donor and is in development as an anticancer drug. Its mechanism of action and effect on cells is not yet fully understood. METHODOLOGY/PRINCIPAL
findingsWe used HPLC and mass spectrometry to identify a primary nitroaromatic glutathione metabolite of PABA/NO and used fluorescent assays to characterize drug effects on calcium and NO homeostasis, relating these to endothelial nitric oxide synthase (eNOS) activity. Unexpectedly, the glutathione conjugate was found to be a competitive inhibitor of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) presumably at the same site as thapsigargin, increasing intracellular Ca2+ release and causing auto-regulation of eNOS through S-glutathionylation. CONCLUSIONS/SIGNIFICANCE: The initial direct release of NO after PABA/NO was followed by an eNOS-mediated generation of NO as a consequence of drug-induced increase in Ca2+ flux and calmodulin (CaM) activation. PABA/NO has a unique dual mechanism of action with direct intracellular NO generation combined with metabolite driven regulation of eNOS activation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.