Translator Disclaimer
1 June 2004 Basic Fibroblast Growth Factor Inhibits Radiation-Induced Apoptosis of HUVECs. II. The RAS/MAPK Pathway and Phosphorylation of BAD at Serine 112
Qingyang Gu, Dewen Wang, Xiaodan Wang, Ruiyun Peng, Jie Liu, Hua Deng, Zhaohai Wang, Tao Jiang
Author Affiliations +
Abstract

Gu, Q., Wang, D., Wang, X., Peng, R., Liu, J., Deng, H., Wang, Z. and Jiang, T. Basic Fibroblast Growth Factor Inhibits Radiation-Induced Apoptosis of HUVECs. II. The RAS/ MAPK Pathway and Phosphorylation of BAD at Serine 112. Radiat. Res. 161, 703–711 (2004).

Radiation-induced endothelial cell apoptosis is involved in the development of many radiation injuries, including radiation-induced skin ulcers. The proangiogenic growth factor basic fibroblast growth factor (bFGF, NUDT6) enhances endothelial cell survival. In the present study, we set up a model of apoptosis in which primary cultured human umbilical vein endothelial cells (HUVECs) were irradiated with 60Co γ rays to explore the effects of bFGF on radiation-induced apoptosis of HUVECs and the signaling pathways involved. We found that bFGF inhibited radiation-induced apoptosis of HUVECs, and that the effect was mediated in part by the RAS/MEK/ MAPK/RSK (p90 ribosomal S6 kinase)/BAD pathway. This pathway was activated by exposure of irradiated HUVECs to bFGF, involving phosphorylation of FGFR, MEK and p44/42 MAPK. The survival-enhancing effect of bFGF was partly inhibited by U0126 and PD98059. The fact that the anti-apoptosis effect of bFGF on irradiated HUVECs was not completely abrogated by U0126 and PD98059 suggests that other survival signaling pathways may exist. Transfection of a dominant-negative form of RSK2 (DN RSK2) partly blocked the anti-apoptosis effect of bFGF in irradiated HUVECs. Moreover, we provide evidence for the first time that bFGF induced BAD phosphorylation (at serine 112) and CREB (cAMP response element-binding protein) activation (phosphorylation at serine 133) in γ-irradiated HUVECs. In our model, inhibition of MAPK signaling-dependent phosphorylation of BAD at serine 112 promoted increased association with BCL-XL, suggesting that MAPK pathway-dependent serine 112 phosphorylation of BAD is critical for the effect of bFGF on cell survival. These results showed that RAS/MAPK/BAD pathway participated in the bFGF-induced effect on survival of HUVECs exposed to radiation. It is suggested that RAS/ MAPK pathway in tumor vascular endothelium could be a potential therapeutic target to enhance the efficacy of ionizing radiation.

Qingyang Gu, Dewen Wang, Xiaodan Wang, Ruiyun Peng, Jie Liu, Hua Deng, Zhaohai Wang, and Tao Jiang "Basic Fibroblast Growth Factor Inhibits Radiation-Induced Apoptosis of HUVECs. II. The RAS/MAPK Pathway and Phosphorylation of BAD at Serine 112," Radiation Research 161(6), 703-711, (1 June 2004). https://doi.org/10.1667/RR3159
Received: 13 June 2003; Accepted: 1 September 2003; Published: 1 June 2004
JOURNAL ARTICLE
9 PAGES


Share
SHARE
RIGHTS & PERMISSIONS
Get copyright permission
Back to Top