| Disruption of Nox2 and TNFRp55/p75 eliminates cardioprotection induced by anisomycin. | |
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MedLine Citation:
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PMID: 22982779 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Transient activation of p38 through anisomycin is demonstrated to precondition the heart against myocardial injury. However, it remains unknown whether specific TNF-α receptor (TNFR) p55/p75 and Nox2, a subunit of NADPH oxidase, are involved in this event. We sought to investigate whether the genetic disruption of TNFRp55/p75 and Nox2 eliminated cardioprotection elicited by anisomycin and whether p38-dependent activation of Nox2 stimulated TNFR to ultimately achieve protective effects. Adult wild-type and TNFR p55/p75(-/-) and Nox2(-/-) mice received intraperitoneal injections of anisomycin (0.1 mg/kg), a potent activator of p38. The hearts were subjected to 30 min myocardial ischemia/30 min reperfusion in the Langendorff perfused heart after 24 h. Left ventricular function was measured, and infarct size was determined. Myocardial TNF-α protein, Nox2, and superoxides releases were detected. Gel kinase assay was employed to detect the effect of p38 on Nox2 phosphorylation. Activation of p38 through anisomycin produces marked improvements in left ventricular functional recovery, and the reduction of myocardial infarction, which were abrogated by disruption of Nox2 and TNFR p55/p75. Disruption of Nox2 and TNFR p55/p75 abolished the effect of anisomycin-induced reduction of infarct size. Anisomycin induced the production of TNF-α, which was abrogated in Nox2(-/-) mice and by treatment with SB203580, but not by disruption of p55/p75. Anisomycin treatment resulted in an increase in Nox2 protein and the phosphorylation of Nox2, which was blocked by inhibition of p38. Taken together, these results indicate that stimulation of the Nox2 and TNFR p55/p75 pathway is a novel approach to anisomycin-induced cardioprotection. |
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Authors:
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Ting C Zhao; Ling Zhang; Jun T Liu; Tai L Guo |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-09-14 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 303 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-16 Completed Date: 2013-01-17 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H1263-72 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, China. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anisomycin / administration & dosage, pharmacology* Disease Models, Animal Enzyme Activation Enzyme Activators / administration & dosage, pharmacology* Injections, Intraperitoneal Male Membrane Glycoproteins / deficiency, genetics, metabolism* Mice Mice, Inbred C57BL Mice, Knockout Myocardial Infarction / drug therapy*, metabolism, pathology, physiopathology Myocardial Reperfusion Injury / drug therapy*, metabolism, pathology, physiopathology Myocardium / metabolism*, pathology NADPH Oxidase / deficiency, genetics, metabolism* Protein Kinase Inhibitors / pharmacology Receptors, Tumor Necrosis Factor, Type I / deficiency, genetics, metabolism* Receptors, Tumor Necrosis Factor, Type II / deficiency, genetics, metabolism* Signal Transduction / drug effects Superoxides / metabolism Time Factors Tumor Necrosis Factor-alpha / metabolism Ventricular Function, Left / drug effects p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01-HL-089405/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Activators; 0/Membrane Glycoproteins; 0/Protein Kinase Inhibitors; 0/Receptors, Tumor Necrosis Factor, Type I; 0/Receptors, Tumor Necrosis Factor, Type II; 0/Tnfrsf1a protein, mouse; 0/Tumor Necrosis Factor-alpha; 11062-77-4/Superoxides; 22862-76-6/Anisomycin; EC 1.6.3.1/Cybb protein, mouse; EC 1.6.3.1/NADPH Oxidase; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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