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dc.contributor.authorNakazawa, Harumasaen_US
dc.contributor.authorChang, Kyunghoen_US
dc.contributor.authorShinozaki, Shoheien_US
dc.contributor.authorYasukawa, Takashien_US
dc.contributor.authorIshimaru, Kazuhiroen_US
dc.contributor.authorYasuhara, Shingoen_US
dc.contributor.authorYu, Yong-Mingen_US
dc.contributor.authorMartyn, J. A. Jeevendraen_US
dc.contributor.authorTompkins, Ronald. G.en_US
dc.contributor.authorShimokado, Kentaroen_US
dc.contributor.authorKaneki, Masaoen_US
dc.date.accessioned2017-03-28T23:49:06Z
dc.date.issued2017en_US
dc.identifier.citationNakazawa, H., K. Chang, S. Shinozaki, T. Yasukawa, K. Ishimaru, S. Yasuhara, Y. Yu, et al. 2017. “iNOS as a Driver of Inflammation and Apoptosis in Mouse Skeletal Muscle after Burn Injury: Possible Involvement of Sirt1 S-Nitrosylation-Mediated Acetylation of p65 NF-κB and p53.” PLoS ONE 12 (1): e0170391. doi:10.1371/journal.pone.0170391. http://dx.doi.org/10.1371/journal.pone.0170391.en
dc.identifier.issnen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:31731717
dc.description.abstractInflammation and apoptosis develop in skeletal muscle after major trauma, including burn injury, and play a pivotal role in insulin resistance and muscle wasting. We and others have shown that inducible nitric oxide synthase (iNOS), a major mediator of inflammation, plays an important role in stress (e.g., burn)-induced insulin resistance. However, it remains to be determined how iNOS induces insulin resistance. Moreover, the interrelation between inflammatory response and apoptosis is poorly understood, although they often develop simultaneously. Nuclear factor (NF)-κB and p53 are key regulators of inflammation and apoptosis, respectively. Sirt1 inhibits p65 NF-κB and p53 by deacetylating these transcription factors. Recently, we have shown that iNOS induces S-nitrosylation of Sirt1, which inactivates Sirt1 and thereby increases acetylation and activity of p65 NF-κB and p53 in various cell types, including skeletal muscle cells. Here, we show that iNOS enhances burn-induced inflammatory response and apoptotic change in mouse skeletal muscle along with S-nitrosylation of Sirt1. Burn injury induced robust expression of iNOS in skeletal muscle and gene disruption of iNOS significantly inhibited burn-induced increases in inflammatory gene expression and apoptotic change. In parallel, burn increased Sirt1 S-nitrosylation and acetylation and DNA-binding capacity of p65 NF-κB and p53, all of which were reversed or ameliorated by iNOS deficiency. These results indicate that iNOS functions not only as a downstream effector but also as an upstream enhancer of burn-induced inflammatory response, at least in part, by Sirt1 S-nitrosylation-dependent activation (acetylation) of p65 NF-κB. Our data suggest that Sirt1 S-nitrosylation may play a role in iNOS-mediated enhanced inflammatory response and apoptotic change, which, in turn, contribute to muscle wasting and supposedly to insulin resistance after burn injury.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0170391en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242494/pdf/en
dash.licenseLAAen_US
dc.subjectBiology and Life Sciencesen
dc.subjectAnatomyen
dc.subjectMusculoskeletal Systemen
dc.subjectMusclesen
dc.subjectSkeletal Musclesen
dc.subjectMedicine and Health Sciencesen
dc.subjectCritical Care and Emergency Medicineen
dc.subjectTrauma Medicineen
dc.subjectTraumatic Injuryen
dc.subjectBurnsen
dc.subjectPhysical Sciencesen
dc.subjectChemistryen
dc.subjectChemical Reactionsen
dc.subjectAcetylationen
dc.subjectBiochemistryen
dc.subjectProteinsen
dc.subjectPost-Translational Modificationen
dc.subjectImmunologyen
dc.subjectImmune Responseen
dc.subjectInflammationen
dc.subjectDiagnostic Medicineen
dc.subjectSigns and Symptomsen
dc.subjectPathology and Laboratory Medicineen
dc.subjectCell Biologyen
dc.subjectCell Processesen
dc.subjectCell Deathen
dc.subjectApoptosisen
dc.subjectEndocrinologyen
dc.subjectEndocrine Physiologyen
dc.subjectInsulin Resistanceen
dc.subjectPhysiologyen
dc.subjectMusculoskeletal Injuryen
dc.subjectS-Nitrosylationen
dc.titleiNOS as a Driver of Inflammation and Apoptosis in Mouse Skeletal Muscle after Burn Injury: Possible Involvement of Sirt1 S-Nitrosylation-Mediated Acetylation of p65 NF-κB and p53en
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorYasuhara, Shingoen_US
dc.date.available2017-03-28T23:49:06Z
dc.identifier.doi10.1371/journal.pone.0170391*
dash.authorsorderedfalse
dash.contributor.affiliatedYu, Yong-Ming
dash.contributor.affiliatedMartyn, J.
dash.contributor.affiliatedYasuhara, Shingo
dash.contributor.affiliatedKaneki, Masao


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