ArticlePloS one2012
Acyloxy nitroso compounds inhibit LIF signaling in endothelial cells and cardiac myocytes: evidence that STAT3 signaling is redox-sensitive.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Oxidative stress induces inflammation of lens cells and triggers immune surveillance of ocular tissues.Chemico-biological interactions · 2022Article
- Pleiotropic, Unique and Shared Responses Elicited by IL-6 Family Cytokines in Human Vascular Endothelial Cells.International journal of molecular sciences · 2022Article
- Bilateral Superior Cervical Sympathectomy Activates Signal Transducer and Activator of Transcription 3 Signal to Alleviate Myocardial Ischemia-Reperfusion Injury.Frontiers in cardiovascular medicine · 2022Article
- Redox Regulation of STAT1 and STAT3 Signaling.International journal of molecular sciences · 2020Review
- Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution.Pharmacological reviews · 2020Review
- Advances in research on treatment of heart failure with nitrosyl hydrogen.Heart failure reviews · 2019Review
- Natural Sesquiterpene Lactones Enhance Chemosensitivity of Tumor Cells through Redox Regulation of STAT3 Signaling.Oxidative medicine and cellular longevity · 2019Review
- STAT3 and Endothelial Cell-Cardiomyocyte Dialog in Cardiac Remodeling.Frontiers in cardiovascular medicine · 2019Review
- Bioinformatic screening for key miRNAs and genes associated with myocardial infarction.FEBS open bio · 2018Article
- Recent Developments on the Crosstalk Between STAT3 and Inflammation in Heart Function and Disease.Frontiers in immunology · 2018Review
- The chemical biology of HNO signaling.Archives of biochemistry and biophysics · 2017Review
- Targeting Obesity and Diabetes to Treat Heart Failure with Preserved Ejection Fraction.Frontiers in endocrinology · 2017Review
- Recent advances in the chemical biology of nitroxyl (HNO) detection and generation.Nitric oxide : biology and chemistry · 2016Review
- Berberine protects rat heart from ischemia/reperfusion injury via activating JAK2/STAT3 signaling and attenuating endoplasmic reticulum stress.Acta pharmacologica Sinica · 2016Article
- Plumericin inhibits proliferation of vascular smooth muscle cells by blocking STAT3 signaling via S-glutathionylation.Scientific reports · 2016Article
- Pivotal Importance of STAT3 in Protecting the Heart from Acute and Chronic Stress: New Advancement and Unresolved Issues.Frontiers in cardiovascular medicine · 2015Review
- Involvement of hypothalamic PI3K-STAT3 signalling in regulating appetite suppression mediated by amphetamine.British journal of pharmacology · 2014Article
- Galiellalactone is a direct inhibitor of the transcription factor STAT3 in prostate cancer cells.The Journal of biological chemistry · 2014Article
- Toward a new STATe: the role of STATs in mitochondrial function.Seminars in immunology · 2014Review
- Direct and nitroxyl (HNO)-mediated reactions of acyloxy nitroso compounds with the thiol-containing proteins glyceraldehyde 3-phosphate dehydrogenase and alkyl hydroperoxide reductase subunit C.Journal of medicinal chemistry · 2013Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 4 countries.
Funding
Abstract
We previously showed that oxidative stress inhibits leukemia inhibitory factor (LIF) signaling by targeting JAK1, and the catalytic domains of JAK 1 and 2 have a cysteine-based redox switch. Thus, we postulated that the NO sibling and thiophylic compound, nitroxyl (HNO), would inhibit LIF-induced JAK-STAT3 activation. Pretreatment of human microvascular endothelial cells (HMEC-1) or neonatal rat cardiomyocytes with the HNO donors Angeli's salt or nitrosocyclohexyl acetate (NCA) inhibited LIF-induced STAT3 activation. NCA pretreatment also blocked the induction of downstream inflammatory genes (e.g. intercellular adhesion molecule 1, CCAAT/enhancer binding protein delta). The related 1-nitrosocyclohexyl pivalate (NCP; not a nitroxyl donor) was equally effective in inhibiting STAT3 activation, suggesting that these compounds act as thiolate targeting electrophiles. The JAK1 redox switch is likely not a target of acyloxy nitroso compounds, as NCA had no effect on JAK1 catalytic activity and only modestly affected JAK1-induced phosphorylation of the LIF receptor. However, pretreatment of recombinant human STAT3 with NCA or NCP reduced labeling of free sulfhydryl residues. We show that NCP in the presence of diamide enhanced STAT3 glutathionylation and dimerization in adult mouse cardiac myocytes and altered STAT3 under non-reducing conditions. Finally, we show that monomeric STAT3 levels are decreased in the Gαq model of heart failure in a redox-sensitive manner. Altogether, our evidence indicates that STAT3 has redox-sensitive cysteines that regulate its activation and are targeted by HNO donors and acyloxy nitroso compounds. These findings raise the possibility of new therapeutic strategies to target STAT3 signaling via a redox-dependent manner, particularly in the context of cardiac and non-cardiac diseases with prominent pro-inflammatory signaling.
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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.