title: Protein kinase C signaling pathway involvement in cardioprotection during isoflurane pretreatment.
abstract: The well‑known cardioprotective effect of isoflurane, a type of volatile anesthetic, against myocardial ischemia/reperfusion (I/R) injury has become an important focus in cardiovascular research. During reperfusion numerous oxidants, such as H2O2, are produced. Aldehyde dehydrogenase 2 (ALDH2) is a protective factor in myocardial I/R, and once phosphorylated and activated ALDH2 may confer cardioprotection. The present study investigated whether cardioprotection by isoflurane depends on the activation of ALDH2 and aimed to determine how protein kinase C (PKC)δ is involved in isoflurane‑induced cardioprotection. Anaesthetized rats were used to produce I/R injury models by imposing 40 min of coronary artery occlusion followed by 120 min of reperfusion. The animals were assigned randomly to the following groups: Untreated controls, and isoflurane preconditioning with and without the PKCδ inhibitor. I/R injury was estimated by the activity of lactate dehydrogenase (LDH) and creatine kinase‑MB (CK‑MB). Isoflurane pretreatment was observed to attenuate the release of LDH and CK‑MB, and enhance the phosphorylation of ALDH2. Activation of ALDH2 and cardioprotection induced by isoflurane preconditioning were enhanced by a PKCδ inhibitor. The results suggest that the activation of ALDH2 by the inhibition of the mitochondrial translocation of PKCδ is important in the protection of the myocardium from I/R injury, and that the effect of PKCδ on isoflurane preconditioning is directly opposed to that of PKCε. PKCε activation was involved in isoflurane pretreatment, which consequently activated downstream signaling pathways and aided cardioprotection. Isoflurane pretreatment also led to attenuated mitochondrial translocation of PKCδ.
authors.affiliation: Department of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, P.R. China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Xiao-E
authors.initials: XE
authors.lastname: Lang
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D052279:Creatine Kinase, MB Form / Q000097:blood / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D007530:Isoflurane / Q000008:administration & dosage / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D002316:Cardiotonic Agents; D007530:Isoflurane; D007770:L-Lactate Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D052279:Creatine Kinase, MB Form