title: Sevoflurane postconditioning protects rat hearts against ischemia-reperfusion injury via the activation of PI3K/AKT/mTOR signaling.
abstract: Phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway plays a key role in myocardial ischemia-reperfusion (I/R) injury. Mammalian target of rapamycin (mTOR), a downstream target of PI3K/AKT signaling, is necessary and sufficient to protect the heart from I/R injury. Inhaled anesthetic sevoflurane is widely used in cardiac surgeries because its induction and recovery are faster and smoother than other inhaled anesthetics. Sevoflurane proved capable of inducing postconditioning effects in the myocardium. However, the underlying molecular mechanisms for sevoflurane-induced postconditioning (SPC) were largely unclear. In the present study, we demonstrated that SPC protects myocardium from I/R injury with narrowed cardiac infarct focus, increased ATP content, and decreased cardiomyocyte apoptosis, which are mainly due to the activation of PI3K/AKT/mTOR signaling and the protection of mitochondrial energy metabolism. Application of dactolisib (BEZ235), a PI3K/mTOR dual inhibitor, abolishes the up-regulation of pho-AKT, pho-GSK, pho-mTOR, and pho-p70s6k induced by SPC, hence abrogating the anti-apoptotic effect of sevoflurane and reducing SPC-mediated protection of heart from I/R injury. As such, this study proved that PI3K/AKT/mTOR pathway plays an important role in SPC induced cardiac protection against I/R injury.
authors.affiliation: Department of Anesthesiology, the Second Affiliate Hospital of Nanchang University, Nanchang, 330000, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, the Second Affiliate Hospital of Soochow University, Suzhou, 215000, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, the Second Affiliate Hospital of Nanchang University, Nanchang, 330000, China.
authors.forename: Shuchun
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Anesthesiology, the Second Affiliate Hospital of Nanchang University, Nanchang, 330000, China.
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Department of Anesthesiology, the Second Affiliate Hospital of Nanchang University, Nanchang, 330000, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, the Second Affiliate Hospital of Nanchang University, Nanchang, 330000, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, the Second Affiliate Hospital of Nanchang University, Nanchang, 330000, China.
authors.forename: Fuzhou
authors.initials: F
authors.lastname: Hua
authors.affiliation: Department of Anesthesiology, the Second Affiliate Hospital of Nanchang University, Nanchang, 330000, China.
authors.forename: Guohai
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Cardiology, the Second Affiliate Hospital of Nanchang University, Nanchang, 330000, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D057775:Ischemic Postconditioning / Q000379:methods; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D008738:Methyl Ethers; D000077149:Sevoflurane; C546845:mTOR protein, rat; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases