Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/61625
Title: Acute treatment of resveratrol alleviates doxorubicin-induced myotoxicity in aged skeletal muscle through SIRT1-dependent mechanisms
Authors: Sin, TK
Tam, BT
Yu, AP
Yip, SP 
Yung, BY 
Chan, LW 
Wong, CS 
Rudd, JA
Siu, PM 
Keywords: Apoptosis
Doxorubicin
Resveratrol
SIRT1
Issue Date: 2016
Publisher: Oxford University Press
Source: Journals of gerontology. Series A, Biological sciences and medical sciences, 2016, v. 71, no. 6, p. 730-739 How to cite?
Journal: Journals of gerontology. Series A, Biological sciences and medical sciences 
Abstract: 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 IRS1Ser307, mTORSer2481, AktThr308/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.
URI: http://hdl.handle.net/10397/61625
ISSN: 1079-5006
EISSN: 1758-535X
DOI: 10.1093/gerona/glv175
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