title: Syntaxin 1A mediates isoflurane but not hypoxia preconditioning-induced alleviation of hypoxia-reoxygenation injury in rat cardiomyocytes.
abstract: Preconditioning with ischemia/hypoxia (IPC/HPC) or clinically available volatile anesthetics such as isoflurane (Iso-PC) could activate cardioprotective signaling pathways, thereby reducing myocardial ischemia/reperfusion (IR) injury. However, their molecular targets remain elusive. We herein investigated the roles of syntaxin 1A (Stx-1A) in cardiomyocyte protection induced by HPC and Iso-PC. Both in vivo myocardial IR model and in vitro cardiomyocyte hypoxia/reoxygenation (HR) model were used to test the effects of IR/HR, IPC/HPC and Iso-PC on Stx-1A protein expression. Stx-1A knockdown and overexpression in cardiomyocytes were achieved by adenovirus infection to define the relationship between Stx-1A levels and IPC/Iso-PC-induced cardioprotection. Cardiac troponin T (cTnT), cell apoptosis rate, and cell viability were introduced as indicators for cardiomyocyte HR injury. Changes of cardioprotective signaling pathways activities including PI3K/AKT/GSK3β, ERK1/2, STAT3 and PKC were also detected using Western blot. Rat cardiomyocyte Stx-1A was upregulated 4 hours after IR or HR. IPC/HPC as well as Iso-PC further increased Stx-1A expression compared with IR/HR. Stx-1A knockdown was accompanied with more cell apoptosis and decreased cell viability while overexpression of Stx-1A seemed cardioprotective. Iso-PC induced decrease in cell apoptosis and increase in cell viability but not HPC-induced cardioprotection was reversed by Stx-1A shRNA transfection. No difference in cell apoptosis or cell viability was found before and after Stx-1A overexpression in each group. Moreover, Stx-1A knockdown were accompanied with increased PI3K/AKT/GSK3β activities irrespective of the treatments. Stx-1A is cardioprotective and a potential target of isoflurane induced cardioprotection. Further studies are needed to test whether stx-1A is regulated by AKT/GSK3β signaling.
authors.affiliation: Department of Anesthesiology, Changzheng Hospital Affiliated to Second Military Medical University Shanghai 200003, China ; Department of Anesthesiology, 401 Hospital of PLA Qingdao 266071, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Second Artillery General Hospital PLA Beijing 100088, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Changzheng Hospital Affiliated to Second Military Medical University Shanghai 200003, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medicine, Second Military Medical University Shanghai 200433, China.
authors.forename: Caiguo
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, Changzheng Hospital Affiliated to Second Military Medical University Shanghai 200003, China ; Department of Anesthesiology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine Shanghai 200092, China.
authors.forename: Xueyin
authors.initials: X
authors.lastname: Shi
keywords: Syntaxin 1A; cardiomyocyte; hypoxia; preconditioning; volatile anesthetics