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Article: Acute Treatment of Resveratrol Alleviates Doxorubicin-Induced Myotoxicity in Aged Skeletal Muscle Through SIRT1-Dependent Mechanisms

TitleAcute Treatment of Resveratrol Alleviates Doxorubicin-Induced Myotoxicity in Aged Skeletal Muscle Through SIRT1-Dependent Mechanisms
Authors
KeywordsDoxorubicin
SIRT1
Apoptosis
Resveratrol
Issue Date2016
Citation
Journals of Gerontology - Series A Biological Sciences and Medical Sciences, 2016, v. 71, n. 6, p. 730-739 How to Cite?
Abstract© 2015 The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. Study of the exacerbating effects of chemotherapeutics, such as doxorubicin, on the impairment of insulin metabolic signaling in aged skeletal muscle is very limited. Here, we tested the hypothesis that activation of sirtuin 1 deacetylase activity by resveratrol would prevent the disruption of insulin signaling and augmentation of catabolic markers induced by doxorubicin in aged skeletal muscle. Two- and 10-month-old senescence-accelerated mice (prone 8) were randomized to receive saline, doxorubicin, doxorubicin and resveratrol, or a combination of doxorubicin, resveratrol, and sirtinol or EX527. Doxorubicin reduced the sirtuin 1 activity without affecting the phosphorylation levels of IRS1 Ser307 , mTOR Ser2481 , Akt Thr308/Ser473 , membranous glucose transporter 4, protein abundance of PDK4, and enzymatic activity of pyruvate dehydrogenase in aged muscles. Intriguingly, resveratrol attenuated the doxorubicin-induced elevations of apoptotic and catabolic markers measured as Bax, caspase 3 activity, apoptotic DNA fragmentation, MuRF-1, ubiquitinated proteins, and proteasomal activity in aged muscles, whereas these beneficial effects were abolished on inhibition of sirtuin 1 by sirtinol or EX527. Markers of insulin signaling were not affected by doxorubicin or resveratrol in the senescent skeletal muscle. Nevertheless, the antiapoptotic and anticatabolic effects of resveratrol in aged skeletal muscle treated with doxorubicin were mediated in a sirtuin 1-dependent signaling manner.
Persistent Identifierhttp://hdl.handle.net/10722/244272
ISSN
2023 Impact Factor: 4.3
2023 SCImago Journal Rankings: 1.285
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSin, Thomas K.-
dc.contributor.authorTam, Bjorn T.-
dc.contributor.authorYu, Angus P.-
dc.contributor.authorYip, Shea P.-
dc.contributor.authorYung, Benjamin Y.-
dc.contributor.authorChan, Lawrence W.-
dc.contributor.authorWong, Cesar S.-
dc.contributor.authorRudd, John A.-
dc.contributor.authorSiu, Parco M.-
dc.date.accessioned2017-08-31T08:56:31Z-
dc.date.available2017-08-31T08:56:31Z-
dc.date.issued2016-
dc.identifier.citationJournals of Gerontology - Series A Biological Sciences and Medical Sciences, 2016, v. 71, n. 6, p. 730-739-
dc.identifier.issn1079-5006-
dc.identifier.urihttp://hdl.handle.net/10722/244272-
dc.description.abstract© 2015 The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. Study of the exacerbating effects of chemotherapeutics, such as doxorubicin, on the impairment of insulin metabolic signaling in aged skeletal muscle is very limited. Here, we tested the hypothesis that activation of sirtuin 1 deacetylase activity by resveratrol would prevent the disruption of insulin signaling and augmentation of catabolic markers induced by doxorubicin in aged skeletal muscle. Two- and 10-month-old senescence-accelerated mice (prone 8) were randomized to receive saline, doxorubicin, doxorubicin and resveratrol, or a combination of doxorubicin, resveratrol, and sirtinol or EX527. Doxorubicin reduced the sirtuin 1 activity without affecting the phosphorylation levels of IRS1 Ser307 , mTOR Ser2481 , Akt Thr308/Ser473 , membranous glucose transporter 4, protein abundance of PDK4, and enzymatic activity of pyruvate dehydrogenase in aged muscles. Intriguingly, resveratrol attenuated the doxorubicin-induced elevations of apoptotic and catabolic markers measured as Bax, caspase 3 activity, apoptotic DNA fragmentation, MuRF-1, ubiquitinated proteins, and proteasomal activity in aged muscles, whereas these beneficial effects were abolished on inhibition of sirtuin 1 by sirtinol or EX527. Markers of insulin signaling were not affected by doxorubicin or resveratrol in the senescent skeletal muscle. Nevertheless, the antiapoptotic and anticatabolic effects of resveratrol in aged skeletal muscle treated with doxorubicin were mediated in a sirtuin 1-dependent signaling manner.-
dc.languageeng-
dc.relation.ispartofJournals of Gerontology - Series A Biological Sciences and Medical Sciences-
dc.subjectDoxorubicin-
dc.subjectSIRT1-
dc.subjectApoptosis-
dc.subjectResveratrol-
dc.titleAcute Treatment of Resveratrol Alleviates Doxorubicin-Induced Myotoxicity in Aged Skeletal Muscle Through SIRT1-Dependent Mechanisms-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1093/gerona/glv175-
dc.identifier.pmid26450947-
dc.identifier.scopuseid_2-s2.0-84973503053-
dc.identifier.volume71-
dc.identifier.issue6-
dc.identifier.spage730-
dc.identifier.epage739-
dc.identifier.eissn1758-535X-
dc.identifier.isiWOS:000377485900004-
dc.identifier.issnl1079-5006-

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