title: bFGF attenuates endoplasmic reticulum stress and mitochondrial injury on myocardial ischaemia/reperfusion via activation of PI3K/Akt/ERK1/2 pathway.
abstract: Extensive research focused on finding effective strategies to prevent or improve recovery from myocardial ischaemia/reperfusion (I/R) injury. Basic fibroblast growth factor (bFGF) has been shown to have therapeutic potential in some heart disorders, including ischaemic injury. In this study, we demonstrate that bFGF administration can inhibit the endoplasmic reticulum (ER) stress and mitochondrial dysfunction induced in the heart in a mouse model of I/R injury. In vitro, bFGF exerts a protective effect by inhibiting the ER stress response and mitochondrial dysfunction proteins that are induced by tert-Butyl hydroperoxide (TBHP) treatment. Both of these in vivo and in vitro effects are related to the activation of two downstream signalling pathways, PI3K/Akt and ERK1/2. Inhibition of these PI3K/Akt and ERK1/2 pathways by specific inhibitors, LY294002 and PD98059, partially reduces the protective effect of bFGF. Taken together, our results indicate that the cardioprotective role of bFGF involves the suppression of ER stress and mitochondrial dysfunction in ischaemic oxidative damage models and oxidative stress-induced H9C2 cell injury; furthermore, these effects underlie the activation of the PI3K/Akt and ERK1/2 signalling pathways.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Jilin University, Changchun, China; School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Zhouguang
authors.initials: Z
authors.lastname: Wang
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Junming
authors.initials: J
authors.lastname: Ye
authors.forename: Xianghong
authors.initials: X
authors.lastname: Lu
authors.forename: Yi
authors.initials: Y
authors.lastname: Cheng
authors.forename: Lijun
authors.initials: L
authors.lastname: Xiang
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Wenke
authors.initials: W
authors.lastname: Feng
authors.forename: Hongxue
authors.initials: H
authors.lastname: Shi
authors.forename: Xichong
authors.initials: X
authors.lastname: Yu
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000627:therapeutic use*; D005419:Flavonoids / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000473:pathology; D009025:Morpholines / Q000494:pharmacology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D020122:tert-Butylhydroperoxide / Q000633:toxicity
chemical_list: D002316:Cardiotonic Agents; D002867:Chromones; D048049:Extracellular Signal-Regulated MAP Kinases; D016222:Fibroblast Growth Factor 2; D005419:Flavonoids; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D020122:tert-Butylhydroperoxide; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: bFGF; endoplasmic reticulum stress; mitochondrial dysfunction; myocardial ischaemia/reperfusion