title: Protective effect of FK506 on myocardial ischemia/reperfusion injury by suppression of CaN and ASK1 signaling circuitry.
abstract: We investigated protective effect of FK506 on rat hearts subjected to ischemia/reperfusion (I/R) injury by regulating CaN and ASK1. Wistar rats were divided into four groups: Ischemia/reperfusion group (I/R), FK506 + Ischemia/reperfusion group (FK506-I/R), sham group, and FK506 + sham group (FK506-sham). Ischemia/reperfusion was achieved by occluding left coronary artery for 30 min and subsequently reperfusing for 120 min. FK506 was administered 15 min before ischemia. Rats in sham group and FK506-sham group were operated only by placing a ligature around the coronary artery, and the blood supply was not blocked. I/R group showed a rapid increase in TUNEL-positive cells and high risks of histopathological changes in damaged cardiac tissues. FK506 reduced the infarct size and inhibited the activation of CaN enzyme in FK506-I/R group. Increase in Bcl-2/Bax ratio in FK506-IR group indicated that FK506 protected myocardium from apoptosis induced by IR. The activity of CaN and ASK1 protein level decreased significantly after I/R injury in FK506-treated I/R heart. FK506 suppresses the activation of CaN and ASK1 through CaN-mediated apoptosis pathway, and ASK1 negatively regulates CaN activity. Suppression of CaN and ASK1 signaling circuitry are involved in protective effect of FK506 on rat myocardium I/R injury.
authors.affiliation: School of Public Health, Jilin University, Changchun, People's Republic of China.
authors.forename: Xing
authors.initials: X
authors.lastname: Feng
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Jinyu
authors.initials: J
authors.lastname: Liu
authors.forename: Minghua
authors.initials: M
authors.lastname: Jin
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Liu
authors.forename: Haiying
authors.initials: H
authors.lastname: Du
authors.forename: Long
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Sun
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019703:Calcineurin / Q000378:metabolism*; D019610:Cytoprotection; D020287:In Situ Nick-End Labeling; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism*; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D016559:Tacrolimus / Q000494:pharmacology*; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D048848:MAP Kinase Kinase Kinase 5; D019703:Calcineurin; D016559:Tacrolimus