Desacyl ghrelin prevents doxorubicin-induced myocardial fibrosis and apoptosis via the GHSR-independent pathway

Pei, Xiao M.; Yung, Benjamin Yat‐Ming; Yip, Shea Ping; Ying, Michael; Benzie, Iris F.F.; Siu, Parco M.

doi:10.1152/ajpendo.00123.2013

Cited by 50 publications

(37 citation statements)

References 67 publications

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“…Enrichment was seen for fibrosis associated genes (Hepatic fibrosis pathway), followed by genes belonging to NRF2-mediated Oxidative Stress Response and Superoxide Radicals Degradation. This is in accordance with the literature since fibrotic processes and oxidative stress are well-known factors for dox cardiotoxicity [54,55]. Interestingly, there was a broad consistency between the modulatory effects of each individual ERA despite their postulated differences in receptor targeting as discussed above.…”

Section: Discussionsupporting

confidence: 91%

Protective effects of endothelin receptor A and B inhibitors against doxorubicin-induced cardiomyopathy

Schwebe

Ameling

Hammer

et al. 2015

Biochemical Pharmacology

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Section: Discussionsupporting

confidence: 91%

Protective effects of endothelin receptor A and B inhibitors against doxorubicin-induced cardiomyopathy

Schwebe

Ameling

Hammer

et al. 2015

Biochemical Pharmacology

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“…Protein fractions were extracted from muscle homogenates as previously described [44]. Forty milligrams of tissue samples was minced and homogenized in ice-cold lysis buffer (10 mmol/ L NaCl, 1.5 mmol/L MgCl 2 , 20 mmol/L HEPES, pH 7.40, 20 % glycerol, 0.1 % Triton X-100, and 1 mM dithiothreitol) in which the homogenates were subject to centrifugation at 875×g for 5 min at 4°C.…”

Section: Protein Fraction Preparationmentioning

confidence: 99%

Unacylated ghrelin restores insulin and autophagic signaling in skeletal muscle of diabetic mice

Tam

Pei

Yung

et al. 2015

Pflugers Arch - Eur J Physiol

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Impairment of insulin signaling in skeletal muscle detrimentally affects insulin-stimulated disposal of glucose. Restoration of insulin signaling in skeletal muscle is important as muscle is one of the major sites for disposal of blood glucose. Recently, unacylated ghrelin (UnAG) has received attention in diabetic research due to its favorable actions on improving glucose tolerance, glycemic control, and insulin sensitivity. The investigation of UnAG has entered phase Ib clinical trial in type 2 diabetes and phase II clinical trial in hyperphagia in Prader-Willi syndrome. Nonetheless, the precise mechanisms responsible for the anti-diabetic actions of UnAG remain incompletely understood. In this study, we examined the effects of UnAG on restoring the impaired insulin signaling in skeletal muscle of db/db diabetic mice. Our results demonstrated that UnAG effectively restored the impaired insulin signaling in diabetic muscle. UnAG decreased insulin receptor substrate (IRS) phosphorylation, increased protein kinase B (Akt) phosphorylation, and, hence, suppressed mTOR signaling. Consequently, UnAG enhanced Glut4 localization and increased PDH activity in the diabetic skeletal muscle. Intriguingly, our data indicated that UnAG normalized the suppressed autophagic signaling in diabetic muscle. In conclusion, our findings illustrated that UnAG restored the impaired insulin and autophagic signaling in skeletal muscle of diabetic mice, which are valuable to understand the underlying mechanisms of the anti-diabetic action of UnAG at peripheral skeletal muscle level.

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“…Echocardiography was performed according to a previously described protocol (Xiao et al, 2014). Animals in each group were anaesthetised with sodium pentobarbital (100 mg/kg).…”

Section: High Frequency Echocardiography Analysismentioning

confidence: 99%

Tanshinone II A Relieves Adriamycin-induced Myocardial Injury in Rat Model

Wang¹,

Chai²,

Wang³

et al. 2015

IJC

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As an effective antineoplastic agent, adriamycin (ADR) remains a use for the treatment of cancer. However, it is limited by the serous cardiotoxicity. Tanshinone II A is the main effective component of Salvia miltiorrhiza Bunge which has been used for treatment of cardiovascular diseases. The purpose of this study is to evaluate the protective effect of Tanshinone II A on adriamycin-induced myocardial injury in rat and explore the mechanism of this effect. Male Wistar rats (200 ± 20 g) were divided into three groups, control (CON) group, adriamycin (ADR) group and ADR + Tanshinone II A (TRA) group. At the end of the 4 week treatment period, cardiac function was evaluated by transthoracic echocardiography. Molecular and cellular measurements were performed in atrial muscle to examine histopathological changes, the formation of fibrosis, Inflammation and apoptosis. Cardiac dysfunction was induced by adriamycin, as indicated by significant decreases in ventricular fractional shortening and ejection fraction. This adriamycin-induced cardiac dysfunction was prevented by the treatment of Tanshinone II A. Adriamycin induced pathological changes and fibrosis, activated apoptosis (increased TUNEL index, apoptotic DNA fragmentation,and caspase-3 activity and decreased Bcl-2/Bax ratio), inflammation and suppressed phosphorylation status (eIF2α and PERK) in atrial. All these molecular and cellular alterations induced by ADR were not found in the rats treated with Tanshinone II A. These findings demonstrate clearly that Tanshinone II A protects the cardiomyocytes against the ADR-induced cardiomyopathy by preventing the activation of cardiac fibrosis and apoptosis, and the effects are probably mediated through ERS pathway.

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Desacyl ghrelin prevents doxorubicin-induced myocardial fibrosis and apoptosis via the GHSR-independent pathway

Abstract: IF, Siu PM. Desacyl ghrelin prevents doxorubicin-induced myocardial fibrosis and apoptosis via the GHSR-independent pathway.

Cited by 50 publications

References 67 publications

Protective effects of endothelin receptor A and B inhibitors against doxorubicin-induced cardiomyopathy

Protective effects of endothelin receptor A and B inhibitors against doxorubicin-induced cardiomyopathy

Unacylated ghrelin restores insulin and autophagic signaling in skeletal muscle of diabetic mice

Tanshinone II A Relieves Adriamycin-induced Myocardial Injury in Rat Model

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