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Isoliquiritigenin attenuates myocardial ischemia reperfusion through autophagy activation mediated by AMPK/mTOR/ULK1 signaling.
Shen, Liying; Zhu, Yingwei; Chen, Zhenfeng; Shen, Feng; Yu, Weiwei; Zhang, Li.
Afiliação
  • Shen L; Department of Cardiology, Huzhou Central Hospital, No. 1558, Sanhuan North Road, Wuxing District, Huzhou, 313000, Zhejiang, China.
  • Zhu Y; Department of Cardiology, Huzhou Central Hospital, No. 1558, Sanhuan North Road, Wuxing District, Huzhou, 313000, Zhejiang, China.
  • Chen Z; Department of Cardiology, Huzhou Central Hospital, No. 1558, Sanhuan North Road, Wuxing District, Huzhou, 313000, Zhejiang, China.
  • Shen F; Department of Cardiology, Huzhou Central Hospital, No. 1558, Sanhuan North Road, Wuxing District, Huzhou, 313000, Zhejiang, China.
  • Yu W; Department of Cardiology, Huzhou Central Hospital, No. 1558, Sanhuan North Road, Wuxing District, Huzhou, 313000, Zhejiang, China.
  • Zhang L; Department of Cardiology, Huzhou Central Hospital, No. 1558, Sanhuan North Road, Wuxing District, Huzhou, 313000, Zhejiang, China. zhanglinbu2010@163.com.
BMC Cardiovasc Disord ; 24(1): 415, 2024 Aug 09.
Article em En | MEDLINE | ID: mdl-39123142
ABSTRACT

BACKGROUND:

Ischemia reperfusion (IR) causes impaired myocardial function, and autophagy activation ameliorates myocardial IR injury. Isoliquiritigenin (ISO) has been found to protect myocardial tissues via AMPK, with exerting anti-tumor property through autophagy activation. This study aims to investigate ISO capacity to attenuate myocardial IR through autophagy activation mediated by AMPK/mTOR/ULK1 signaling.

METHODS:

ISO effects were explored by SD rats and H9c2 cells. IR rats and IR-induced H9c2 cell models were established by ligating left anterior descending (LAD) coronary artery and hypoxia/re-oxygenation, respectively, followed by low, medium and high dosages of ISO intervention (Rats 10, 20, and 40 mg/kg; H9c2 cells 1, 10, and 100 µmol/L). Myocardial tissue injury in rats was assessed by myocardial function-related index, HE staining, Masson trichrome staining, TTC staining, and ELISA. Autophagy of H9c2 cells was detected by transmission electron microscopy (TEM) and immunofluorescence. Autophagy-related and AMPK/mTOR/ULK1 pathway-related protein expressions were detected with western blot.

RESULTS:

ISO treatment caused myocardial function improvement, and inhibition of myocardial inflammatory infiltration, fibrosis, infarct area, oxidative stress, CK-MB, cTnI, and cTnT expression in IR rats. In IR-modeled H9c2 cells, ISO treatment lowered apoptosis rate and activated autophagy and LC3 fluorescence expression. In vivo and in vitro, ISO intervention exhibited enhanced Beclin1, LC3II/LC3I, and p-AMPK/AMPK levels, whereas inhibited P62, p-mTOR/mTOR and p-ULK1(S757)/ULK1 protein expression, activating autophagy and protecting myocardial tissues from IR injury.

CONCLUSION:

ISO treatment may induce autophagy by regulating AMPK/mTOR/ULK1 signaling, thereby improving myocardial IR injury, as a potential candidate for treatment of myocardial IR injury.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autofagia / Traumatismo por Reperfusão Miocárdica / Transdução de Sinais / Ratos Sprague-Dawley / Miócitos Cardíacos / Chalconas / Proteínas Quinases Ativadas por AMP / Serina-Treonina Quinases TOR / Proteína Homóloga à Proteína-1 Relacionada à Autofagia Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autofagia / Traumatismo por Reperfusão Miocárdica / Transdução de Sinais / Ratos Sprague-Dawley / Miócitos Cardíacos / Chalconas / Proteínas Quinases Ativadas por AMP / Serina-Treonina Quinases TOR / Proteína Homóloga à Proteína-1 Relacionada à Autofagia Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article