ESMOLOL PROTECTS AGAINST LPS-INDUCED CARDIAC INJURY VIA THE AMPK/mTOR/ULK1 PATHWAY IN RAT

Abstract

The purpose of this study was to investigate the effect of esmolol (ES) on LPS-induced cardiac injury and the possible mechanism. Methods: Sepsis was induced by i.p. injection of LPS (10 mg/kg) in male Sprague-Dawley rats pretreated with ES, 3-methyladenine or rapamycin. The severity of myocardial damage was analyzed by hematoxylin-eosin staining, and myocardial damage scores were calculated. The concentration of cardiac troponin was measured by enzyme-linked immunosorbent assay. The expression of autophagy-related proteins (beclin-1, LC3-II, p-AMPK, p-ULK1, p-mTOR) in myocardial tissue was detected by Western blotting. Autophagosome formation and the ultrastructural damage of mitochondria were assessed using transmission electron microscopy. Results: LPS induced an increase in myocardial damage score in a time-dependent manner, accompanied with an increase in autophagy at 3 h and decrease in autophagy at 6, 12, and 24 h. Pretreatment of LPS-treated rats with ES or rapamycin reduced myocardial injury (release of cardiac troponin, myocardial damage score) and increased autophagy (LC3-II, beclin-1, p-AMPK, and p-ULK1 levels and autophagosome numbers) at 12 and 24 h. In contrast, 3-methyladenine showed no effect. Conclusion: Esmolol alleviates LPS-induced myocardial damage through activating the AMPK/mTOR/ULK1 signal pathway-regulated autophagy.

METFORMIN MITIGATES SEPSIS-ASSOCIATED PULMONARY FIBROSIS BY PROMOTING AMPK ACTIVATION AND INHIBITING HIF-1α–INDUCED AEROBIC GLYCOLYSIS

“…Wang et al (37) reported that phosphorylation of AMPK alleviated mitochondrial damage in renal tissue and ameliorated septic acute kidney injury. Lipopolysaccharide-induced cardiac injury is also abolished by esmolol through increased levels of p-AMPK in the rat (38). AMPKα1, a critical modulator of mitochondrial function, has been shown to be protective in hemorrhagic shock (39).…”

Genetic polymorphisms, biomarkers and signaling pathways associated with septic shock: from diagnosis to therapeutic targets

“…The mTOR–Akt-inositol-requiring enzyme 1α-JNK signaling pathway mediates endoplasmic reticulum stress-induced CD4+ T-cell apoptosis in septic mice [ 145 ] ( Figure 1 ). Esmolol, which is used to treat heart failure, alleviates myocardial injury induced by LPS by activating autophagy regulated by the adenosine monophosphate-activated protein kinase/mTOR/ULK1 signaling pathway [ 146 ]. ERK and PI3K phosphorylate mTOR, which controls cMaf translation in response to LPS-induced TLR4 signaling.…”