ACTIVATION OF KLOTHO/SIRT1 SIGNALING PATHWAY ATTENUATES MYOCARDIAL ISCHEMIA REPERFUSION INJURY IN DIABETIC RATS.
Shock
; 62(3): 447-456, 2024 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-38904464
ABSTRACT
ABSTRACT Diabetes and myocardial ischemia reperfusion (MIR) injury are characterized by oxidative stress, inflammation, autophagy disorders, and cardiac contractile dysfunction. Klotho and SIRT1 regulate the level of oxidative stress to participate in the regulation of many physiological functions such as cell survival, aging, apoptosis, autophagy, mitochondrial biogenesis, and inflammation. We hypothesized that the activation of Klotho/SIRT1 signaling pathway could attenuate MIR in diabetic rats. Type 1 diabetes and MIR injury model were established to examine this hypothesis in vivo . Primary rat cardiomyocytes and H9c2 cells were exposed to high glucose conditions and hypoxia/reoxygenation (H/R) insult in vitro . Hemodynamic parameters of heart function, myocardial infarct size, oxidative stress, markers of MIR injury or cell viability, and the mRNA and protein expression of Klotho and SIRT1 were measured. There was lower expression of Klotho and SIRT1 in diabetic MIR hearts than in nondiabetic rats, as well as significantly increased oxidative stress levels and decreased autophagy levels. Recombinant Klotho (rKlotho) protein and the SIRT1 agonist SRT1720 could significantly attenuate MIR injury in diabetes by activating Klotho/SIRT1 signaling pathway to reduce oxidative stress and restore autophagy levels. These findings suggest that the Klotho/SIRT1 pathway plays an important role in MIR injury in diabetic rats, and rKlotho protein and agonist SRT1720 have therapeutic potential for alleviating diabetic myocardial IR injury by activating Klotho/SIRT1 to reduce oxidative stress and restore autophagy levels.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão Miocárdica
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Transdução de Sinais
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Ratos Sprague-Dawley
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Estresse Oxidativo
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Miócitos Cardíacos
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Diabetes Mellitus Experimental
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Sirtuína 1
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Proteínas Klotho
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Glucuronidase
Limite:
Animals
Idioma:
En
Revista:
Shock
Assunto da revista:
ANGIOLOGIA
/
CARDIOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Estados Unidos