Insulin in combination with selenium inhibits HG/Pal-induced cardiomyocyte apoptosis by Cbl-b regulating p38MAPK/CBP/Ku70 pathway

T.-J. Xu, Y. Liu, P. Li, X.L. Xu, J.R. Zeng

Department of Pharmacology, Xi’an Medical University, Xi’an, Shaanxi, PR China. e-mail: xtj1118@163.com

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• Pharmacology

OBJECTIVE: In this study, we investigated whether insulin and selenium in combination (In/Se) suppresses cardiomyocyte apoptosis and whether this protection is mediated by Cbl-b regulating p38MAPK/CBP/Ku70 pathway.

MATERIALS AND METHODS: Firstly, H9c2 cardiomyocytes were treatment with high glucose (25 mmol/L) and palmitate (600 μmol/L) (HG/Pal). Next, H9c2 cardiomyocytes were treatment with HG/Pal+In/Se (10 nmol/L Insulin in combination with 10 nmol/L selenium). Finally, cells were treated with siRNA against Cbl-b, followed by HG/Pal and HG/Pal+In/Se treatment. Then, Cell apoptosis was observed by flow cytometry (FCM). The levels of Cbl-b, p-p38MAPK, CBP and Bax were examined by Western blotting. The acetylated Ku70 was detected by immunoprecipitation.

RESULTS: Insulin and selenium in combination reduced cell apoptosis, up-regulated Cbl-b expression, down-regulated p38MAPK, CBP and acetylated Ku70 expressions and prevented Bax translocation, whereas Cbl-b knockdown strongly suppressed In/Se-induced these effects in HG/Pal-treated cardiomyocytes.

CONCLUSIONS: Insulin and selenium synergistically suppressed cardiomyocyte apoptosis by Cbl-b regulating p38MAPK/CBP/Ku70 pathway.

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