{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:41:05Z","timestamp":1791225665782,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,4,2]],"date-time":"2014-04-02T00:00:00Z","timestamp":1396396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Doxorubicin, a potent chemotherapeutic drug, has been demonstrated previously as an inducer of apoptosis in muscle cells. Extensive induction of apoptosis may cause excessive loss of muscle cells and subsequent functional decline in skeletal muscle. This study examined the effects of acylated ghrelin, a potential agent for treating cancer cachexia, on inhibiting apoptotic signalling in doxorubicin\u2010treated skeletal muscle. Unacylated ghrelin, a form of ghrelin that does not bind to <jats:styled-content style=\"fixed-case\">GHSR<\/jats:styled-content>\u20101a, is also employed in this study to examine the <jats:styled-content style=\"fixed-case\">GHSR<\/jats:styled-content>\u20101a signalling dependency of the effects of ghrelin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6 mice were randomly assigned to saline control (<jats:styled-content style=\"fixed-case\">CON<\/jats:styled-content>), doxorubicin (<jats:styled-content style=\"fixed-case\">DOX<\/jats:styled-content>), doxorubicin with treatment of acylated ghrelin (<jats:styled-content style=\"fixed-case\">DOX<\/jats:styled-content>+Acylated Ghrelin) and doxorubicin with treatment of unacylated ghrelin (<jats:styled-content style=\"fixed-case\">DOX<\/jats:styled-content>+Unacylated Ghrelin). Mice in all groups that involved <jats:styled-content style=\"fixed-case\">DOX<\/jats:styled-content> were intraperitoneally injected with 15\u00a0mg of doxorubicin per kg body weight, whereas mice in <jats:styled-content style=\"fixed-case\">CON<\/jats:styled-content> group received saline as placebo. Gastrocnemius muscle tissues were harvested after the experimental period for analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The elevation of apoptotic <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> fragmentation and number of <jats:styled-content style=\"fixed-case\">TUNEL<\/jats:styled-content>\u2010positive nuclei were accompanied with the upregulation of Bax in muscle after exposure to doxorubicin, but all these changes were neither seen in the muscle treated with acylated ghrelin nor unacylated ghrelin after doxorubicin exposure. Protein abundances of autophagic markers including <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>3 <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>\u2010to\u2010<jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>3 I ratio, Atg12\u20105 complex, Atg5 and Beclin\u20101 were not altered by doxorubicin but were upregulated by the treatment of either acylated or unacyated ghrelin. Histological analysis revealed that the amount of centronucleated myofibres was elevated in doxorubicin\u2010treated muscle while muscle of others groups showed normal histology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Collectively, our data demonstrated that acylated ghrelin administration suppresses the doxorubicin\u2010induced activation of apoptosis and enhances the cellular signalling of autophagy. The treatment of unacylated ghrelin has similar effects as acylated ghrelin on apoptotic and autophagic signalling, suggesting that the effects of ghrelin are probably mediated through a signalling pathway that is independent of <jats:styled-content style=\"fixed-case\">GHSR<\/jats:styled-content>\u20101a. These findings were consistent with the hypothesis that acylated ghrelin inhibits doxorubicin\u2010induced upregulation of apoptosis in skeletal muscle while treatment of unacylated ghrelin can achieve similar effects as the treatment of acylated ghrelin. The inhibition of apoptosis and enhancement of autophagy induced by acylated and unacylated ghrelin might exert myoprotective effects on doxorubicin\u2010induced toxicity in skeletal muscle.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.12263","type":"journal-article","created":{"date-parts":[[2014,3,3]],"date-time":"2014-03-03T10:54:58Z","timestamp":1393844098000},"page":"201-213","source":"Crossref","is-referenced-by-count":53,"title":["Acylated and unacylated ghrelin inhibit doxorubicin\u2010induced apoptosis in skeletal muscle"],"prefix":"10.1111","volume":"211","author":[{"given":"A. P.","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Health Technology and Informatics The Hong Kong Polytechnic University Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X. 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