title: Delayed cardioprotection by sevoflurane preconditioning: a novel mechanism via inhibiting Beclin 1-mediated autophagic cell death in cardiac myocytes exposed to hypoxia/reoxygenation injury.
abstract: Sevoflurane preconditioning has shown to exert delayed caridioprotection against subsequent ischemia and reperfusion injury, but the mechanisms underlying is unclear. Inhibition of autophagy by 3-methyladenine (3-MA) or knockdown of Beclin 1 leads to enhanced cardiac myocyte survival. Our study aimed to test whether sevoflurane preconditioning provides a second window of anesthetic preconditioning (SWOP) via inhibit Beclin 1-mediated autophagic cell death. H9c2 rat cardiomyocytes were randomly divided into five groups: Control (CON) group; hypoxia/reoxygenation (H/R) group, rat cardiomyocytes was exposed in the airtight container for 2 h followed by 1 h of reoxgenation; SWOP group, rat cardiomyocytes was exposed to 1 h of 2.5% sevoflurane 24 h before H/R; Autophagic inhibitors, 3-methyladenine (3-MA, 10 mM) was added to culture medium 15 min before sevoflurane exposure (3-MA+SWOP group) or cells were treated by 3-MA alone (3-MA group). The cell proliferation was significantly increased in SWOP group (79.49 ± 1.37%, P < 0.05) when compared to H/R group (62.2 ± 6.49%, P < 0.05). 3-MA administered before SWOP significantly attenuated the H/R induced autophagy and cell death. H/R injury up-regulated the expression of LC3-II and Beclin 1 proteins (342 ± 66% and 163 ± 18%, respectively, P < 0.05) compared to the CON group (100%), which were increased in SWOP group (202 ± 77% and 128 ± 8%, respectively, P < 0.05). The expression of LC3-II and Beclin 1 proteins was decreased in 3-MA group (110 ± 28% and 97 ± 6%, respectively) and 3-MA+SWOP group (93 ± 7% and 98 ± 6%, respectively) compared with H/R group, but Bcl-2 was upregulated in 3-MA group (158 ± 4%) and 3-MA+SWOP group (156 ± 5%) compared to H/R group (103 ± 7%). In conclusion, sevoflurane preconditioning confers delayed cardioprotection via inhibition Beclin 1-mediated autophagic cell death in cardiac myocytes 24 h before exposed to H/R injury.
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital of Soochow University Suzhou 215004, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital to Nanchang University Nanchang 330006, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital of Soochow University Suzhou 215004, China.
authors.forename: Shigang
authors.initials: S
authors.lastname: Qiao
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital of Soochow University Suzhou 215004, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology and Critical Care, Second Affiliated Hospital of Soochow University Suzhou 215004, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1; D015153:Blotting, Western; D002460:Cell Line; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008738:Methyl Ethers / Q000494:pharmacology*; D046529:Microscopy, Electron, Transmission; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D000077149:Sevoflurane
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C512829:Becn1 protein, rat; D008738:Methyl Ethers; D010975:Platelet Aggregation Inhibitors; D000077149:Sevoflurane
keywords: Autophagy; Beclin 1; hypoxia/reoxgenation; sevoflurane