Berberine inhibits excessive autophagy and protects myocardium against ischemia/reperfusion injury via the RhoE/AMPK pathway.
Int J Mol Med
; 53(5)2024 05.
Article
em En
| MEDLINE
| ID: mdl-38577949
ABSTRACT
Several studies have shown that berberine (BBR) is effective in protecting against myocardial ischemiareperfusion injury (MI/RI). However, the precise molecular mechanism remains elusive. The present study observed the mechanism and the safeguarding effect of BBR against hypoxia/reoxygenation (H/R) myocardial injury in H9c2 cells. BBR pretreatment significantly improved the decrease of cell viability, P62 protein, Rho Family GTPase 3 (RhoE) protein, ubiquinone subunit B8 protein, ubiquinolcytochrome c reductase core protein U, the Bcl2associated X protein/Bcell lymphoma 2 ratio, glutathione (GSH) and the GSH/glutathione disulphide (GSSG) ratio induced by H/R, while reducing the increase in lactate dehydrogenase, microtubuleassociated protein 1 light 3 protein, caspase3 activity, reactive oxygen species, GSSG and malonaldehyde caused by H/R. Transmission electron microscopy and LysoTracker Red DND99 staining results showed that BBR pretreatment inhibited H/Rinduced excessive autophagy by mediating RhoE. BBR also inhibited mitochondrial permeability transition, maintained the stability of the mitochondrial membrane potential, reduced the apoptotic rate, and increased the level of caspase3. However, the protective effects of BBR were attenuated by pAD/RhoEsmall hairpin RNA, rapamycin (an autophagy activator) and compound C (an AMPactivated protein kinase inhibitor). These new findings suggested that BBR protects the myocardium from MI/RI by inhibiting excessive autophagy, maintaining mitochondrial function, improving the energy supply and redox homeostasis, and attenuating apoptosis through the RhoE/AMPactivated protein kinase pathway.
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Base de dados:
MEDLINE
Assunto principal:
Autofagia
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Berberina
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Traumatismo por Reperfusão Miocárdica
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Proteínas Quinases Ativadas por AMP
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article