Dehydroepiandrosterone (DHEA) modulates sensitivity to radiation-induced injury in human neuroglioma cells (H4) through effects on Akt signalling by glutathione (GSH)-dependent redox regulation. Previous treatment of H4 cells with DHEA for 18 h reduced the gamma-ray-induced phosphorylation of Akt, activated p21(waf1) synthesis and up-regulated phosphorylation of Rb independent of p53. These reactions were followed by a decrease in cell number and an increase in apoptosis and G(2)/M checkpoint arrest. The suppression of phosphorylation of Akt by DHEA was due to regulation of the dephosphorylation by protein phosphatase 2A (PP2A). DHEA up-regulated the expression of gamma-glutamylcysteine synthetase, a rate-limiting enzyme of glutathione (GSH) synthesis, and the levels of GSH to maintain PP2A activity. The results suggested that DHEA increases the sensitivity of cells to gamma-ray irradiation by inducing apoptosis and cell cycle arrest through GSH-dependent regulation of the reduced form of PP2A to down-regulate the Akt signalling pathway.
雑誌名
Free radical research
巻
42
号
11-12
ページ
957 - 965
発行年
2008-11
出版者
Taylor & Francis
ISSN
10715762
PubMed番号
19031317
DOI
10.1080/10715760802566582
権利
c 2008 Informa plc
This is an electronic version of an article published in Free Radical Research, 42(11-12), 957-965: 2008 November. Free Radical Research is available online at: http://www.informaworld.com/openurl?genre=article&issn=10715762&volume=42&issue=11&spage=957
Dehydroepiandrosterone augments sensitivity to gamma-ray irradiation in human H4 neuroglioma cells through down-regulation of Akt signaling.
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