bFGF attenuates endoplasmic reticulum stress and mitochondrial injury on myocardial ischaemia/reperfusion via activation of PI3K/Akt/ERK1/2 pathway

• Published in: Journal of cellular and molecular medicine 2015-03, Vol.19 (3), p.595-607
• Main Authors: Wang, Zhouguang, Wang, Yue, Ye, Junming, Lu, Xianghong, Cheng, Yi, Xiang, Lijun, Chen, Li, Feng, Wenke, Shi, Hongxue, Yu, Xichong, Lin, Li, Zhang, Hongyu, Xiao, Jian, Li, Xiaokun
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; bFGF; Cardiotonic Agents - pharmacology; Cardiotonic Agents - therapeutic use; Cell Line; Chromones - pharmacology; endoplasmic reticulum stress; Endoplasmic Reticulum Stress - drug effects; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors; Extracellular Signal-Regulated MAP Kinases - metabolism; Fibroblast Growth Factor 2 - pharmacology; Fibroblast Growth Factor 2 - therapeutic use; Flavonoids - pharmacology; Male; MAP Kinase Signaling System - drug effects; Mice; Mice, Inbred C57BL; Mitochondria - pathology; mitochondrial dysfunction; Morpholines - pharmacology; myocardial ischaemia/reperfusion; Myocardial Reperfusion Injury - drug therapy; Myocardial Reperfusion Injury - pathology; Original; Oxidative Stress - drug effects; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; Rats; tert-Butylhydroperoxide - toxicity
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.12346

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.