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J Mol Cell Cardiol ; 124: 26-34, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30292723

RESUMO

The effects of curcumin on regulating cardiac apoptosis and autophagy were analyzed in diabetic models both in vivo and in vitro. In vivo, experimental diabetes was induced in mice by low-dose STZ injection combined with a high-fat diet. In vitro, cultured H9c2 cardiomyoblasts were exposed to high d-glucose concentrations combined with palmitate. Our results showed that apoptosis was increased and autophagy was suppressed in the hearts of diabetic mice, which was ameliorated by curcumin treatment, ultimately improving cardiac function. Moreover, the inhibition of autophagy exacerbated apoptotic death in cardiac cells under diabetic condition. Curcumin activated AMPK and JNK1, which phosphorylated Bcl-2 and Bim and subsequently disrupted their interactions with Beclin1, thereby promoting autophagy and alleviating apoptosis respectively. In addition, AMPK-mediated inhibition of mTORC1 pathway likely played a role in regulating autophagy by curcumin under diabetic condition. Our study suggests that curcumin protects against diabetic cardiomyopathy by modulating the crosstalk between autophagic and apoptotic machinery. Modulation of autophagy may be an effective strategy for the treatment of cardiovascular diseases associated with diabetes.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Curcumina/farmacologia , Cardiomiopatias Diabéticas/metabolismo , Substâncias Protetoras/farmacologia , Animais , Biomarcadores , Linhagem Celular , Diabetes Mellitus Experimental , Cardiomiopatias Diabéticas/diagnóstico , Cardiomiopatias Diabéticas/tratamento farmacológico , Modelos Animais de Doenças , Ecocardiografia , Testes de Função Cardíaca , Sistema de Sinalização das MAP Quinases , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Miocárdio/metabolismo , Miocárdio/ultraestrutura , Fosforilação , Ratos , Transdução de Sinais/efeitos dos fármacos
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