title: PI3K/Akt/FoxO3a signaling mediates cardioprotection of FGF-2 against hydrogen peroxide-induced apoptosis in H9c2 cells.
abstract: Cardiovascular disease is a growing major global public health problem. Oxidative stress is regarded as one of the key regulators of pathological physiology, which eventually leads to cardiovascular disease. However, mechanisms by which FGF-2 rescues cells from oxidative stress damage in cardiovascular disease is not fully elucidated. Herein this study was designed to investigate the protective effects of FGF-2 in H2O2-induced apoptosis of H9c2 cardiomyocytes, as well as the possible signaling pathway involved. Apoptosis of H9c2 cardiomyocytes was induced by H2O2 and assessed using methyl thiazolyl tetrazolium assay, Hoechst, and TUNEL staining. Cells were pretreated with PI3K/Akt inhibitor LY294002 to investigate the possible PI3K/Akt pathways involved in the protection of FGF-2. The levels of p-Akt, p-FoxO3a, and Bim were detected by immunoblotting. Stimulation with H2O2 decreased the phosphorylation of Akt and FoxO3a, and induced nuclear localization of FoxO3a and apoptosis of H9c2 cells. These effects of H2O2 were abrogated by pretreatment with FGF-2. Furthermore, the protective effects of FGF-2 were abolished by PI3K/Akt inhibitor LY294002. In conclusion, our data suggest that FGF-2 protects against H2O2-induced apoptosis of H9c2 cardiomyocytes via activation of the PI3K/Akt/FoxO3a pathway.
authors.affiliation: Institute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan Province, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China.|Department of Clinical Laboratory, Affiliated Nanhua Hospital, University of South China, Hengyang, 421001, Hunan, People's Republic of China.
authors.forename: Mi-Hua
authors.initials: MH
authors.lastname: Liu
authors.affiliation: Institute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan Province, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China.
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan Province, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China.|Department of Science and Education, The Pediatric Academy of University of South China, Changsha, Hunan, 410007, People's Republic of China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Peng
authors.affiliation: Institute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan Province, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China.
authors.forename: Shun-Lin
authors.initials: SL
authors.lastname: Qu
authors.affiliation: Department of Pathology, Affiliated Mawangdui Hospital, University of South China, Changsha, Hunan, 410016, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan Province, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Peng
authors.affiliation: Institute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan Province, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China.
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Luo
authors.affiliation: Department of Cardiology/Cardiac Catheterisation Lab, Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People's Republic of China.
authors.forename: Heng-Jing
authors.initials: HJ
authors.lastname: Hu
authors.affiliation: Institute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan Province, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Ren
authors.affiliation: Chuanshan College, University of South China, Hengyang, 421001, Hunan, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan Province, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tang
authors.affiliation: Institute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan Province, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China.
authors.forename: Lu-Shan
authors.initials: LS
authors.lastname: Liu
authors.affiliation: Institute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan Province, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China. tangzhihan98@163.com.
authors.forename: Zhi-Han
authors.initials: ZH
authors.lastname: Tang
authors.affiliation: Institute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan Province, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China. zsjianglab@aliyun.com.
authors.forename: Zhi-Sheng
authors.initials: ZS
authors.lastname: Jiang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000072224:Bcl-2-Like Protein 11 / Q000378:metabolism; D002460:Cell Line; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D000071316:Forkhead Box Protein O3 / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000633:toxicity*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats
chemical_list: D000072224:Bcl-2-Like Protein 11; D016222:Fibroblast Growth Factor 2; D000071316:Forkhead Box Protein O3; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C000606778:Bcl2l11 protein, rat; C499515:FOXO3 protein, rat
keywords: Akt; Apoptosis; Cardiomyocytes; FGF-2; Forkhead transcription factor