Sevoflurane Ameliorates Myocardial Cell Injury by Inducing Autophagy via the Deacetylation of LC3 by SIRT1

Abstract

Misfolded and aberrant proteins have been found to be associated with myocardial cell injury. Thus, increased clearance of misfolded or aggregated proteins via autophagy might be a potential option in preventing myocardial cell injury. Sevoflurane may ameliorate myocardial cell injury by affecting sirtuin 1-(SIRT1-) mediated autophagy. Rat models with myocardial cell injury were induced by limb ischemia reperfusion. The model rats received different treatments: sevoflurane, nicotinamide, and autophagy inhibitor 3-methyladenine (3-MA). Autophagy was observed by SEM. The levels of SIRT1 and microtubuleassociated protein 1A/1B-light chain 3 (LC3) were measured. Present findings demonstrated that limb ischemia reperfusion induced autophagy. Sevoflurane increased the level of SIRT1, which deacetylated LC3 and further increased autophagic rates. On the other hand, the autophagy was inhibited by sevoflurane and or the inhibitors of SIRT1 and LC3. Present results demonstrated a novel molecular mechanism by which sevoflurane induced autophagy by increasing the level of SIRT1 and reducing the acetylation of LC3.

Sevoflurane postconditioning protects against myocardial ischemia/reperfusion injury by restoring autophagic flux via an NO-dependent mechanism

“…In cardiac I/R injury, mitochondrial dysfunction induces autophagosome accumulation, thus contributing to cardiomyocyte death [11]. Although previous reports have shown that sevoflurane postconditioning (SPC) restored autophagic flux in the myocardium and thus provided cardioprotection [12,13], the precise mechanism requires further elucidation.…”

Sirtuin 1 promotes autophagy and proliferation of endometrial cancer cells by reducing acetylation level of LC3

“…Hence, we used serum‐free medium to starve EC cells, and found that the level of LC3‐II/LC3‐I in EC cells was increased, while the expression of p62 was decreased significantly. LC3, viewed as a membrane of APs, exerts crucial effects on cellular apoptosis and autophagy (Fan et al, 2017). LC3‐II/LC3‐I is considered to be a marker of autophagy (Gong et al, 2020).…”

“…Activated SIRT1 promotes autophagy of chondrocytes through deacetylation of lysine residues on key autophagy proteins (Sacitharan et al, 2020). Fan et al have also showed that sevoflurane can induce autophagy by increasing SIRT1 expression and decreasing LC3 acetylation level, thereby reducing myocardial cell injury (Fan et al, 2017). In addition, in vivo experiment exhibited that overexpression of SIRT1 promoted the growth and autophagy of transplanted tumors in nude mice.…”

Follicle‐stimulating hormone regulates glycolysis of water buffalo follicular granulosa cells through AMPK/SIRT1 signalling pathway

“…Studies have shown that SIRT1 can be activated when cells are in starvation state, while cells without serum are in a state of starvation, and SIRT1 is able to maintain cell homeostasis (Chang et al., 2015; Lee et al., 2008). Sirt1 is activated during cell starvation and forms a complex with Atg5, Atg7 and Atg8 (LC3 in mammals), leading to deacetylation of these key autophagy components (Fan et al., 2017; Huang et al., 2015). The function of deacetylase SIRT1 is different in different cells, and the expression conditions of SIRT1 in hypoxia and normoxia state change accordingly due to the changes of nutritional factors and other conditions.…”