title: Basic fibroblast growth factor inhibits radiation-induced apoptosis of HUVECs. I. The PI3K/AKT pathway and induction of phosphorylation of BAD.
abstract: Radiation-induced endothelial cell apoptosis is involved in the development of many radiation injuries, including radiation-induced skin ulcers. The proangiogenic growth factors basic fibroblast growth factor (bFGF, NUDT6) and VEGF enhance endothelial cell survival. In the present study, we used primary cultured human umbilical vein endothelial cells (HUVECs) irradiated with (60)Co gamma rays to explore the effects of bFGF on radiation-induced apoptosis of HUVECs and its signaling pathways. We found that bFGF inhibited radiation-induced apoptosis of HUVECs, and that the effect was mediated by the PI3K/AKT pathway. This pathway was activated by exposure of irradiated HUVECs to bFGF, involving phosphorylation of FGFR, PI3K and AKT. The survival-enhancing effect of bFGF was abrogated by wortmannin and LY294002. Transfection of a dominant-negative mutant of AKT completely blocked the anti-apoptosis effect of bFGF in irradiated HUVECs. We also found evidence for the first time that bFGF induced BAD phosphorylation in the gamma-irradiated HUVECs. These results showed that the PI3K/AKT pathway participated in the bFGF-induced modulation of the survival of irradiated HUVECs. Activation of the PI3K/AKT pathway plays an important role in bFGF-induced endothelial cell survival in the treatment of radiation-induced skin ulcers.
authors.affiliation: Department of Pathology, Beijing Institute of Radiation Medicine, Beijing, China. Guqy2003@yahoo.com.cn
authors.forename: Qingyang
authors.initials: Q
authors.lastname: Gu
authors.forename: Dewen
authors.initials: D
authors.lastname: Wang
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Wang
authors.forename: Ruiyun
authors.initials: R
authors.lastname: Peng
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Zhaohai
authors.initials: Z
authors.lastname: Wang
authors.forename: Shuiming
authors.initials: S
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Deng
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D002352:Carrier Proteins / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D005720:Gamma Rays; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D011836:Radiation Tolerance / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D051025:bcl-Associated Death Protein
chemical_list: D002352:Carrier Proteins; D016222:Fibroblast Growth Factor 2; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D051025:bcl-Associated Death Protein; C494819:BAD protein, human; C494918:AKT1 protein, human