Dehydroepiandrosterone augments sensitivity to γ-ray irradiation in human H4 neuroglioma cells through down-regulation of Akt signaling

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 γ-ray-induced phosphorylation of Akt, activ...

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Published in:Free radical research 2008-11, Vol.42 (11-12), p.957-965
Main Authors: Hirao, Tomohito, Urata, Yoshishige, Kageyama, Kan, Ikezaki, Midori, Kawakatsu, Miho, Matsuse, Michiko, Matsuo, Takayuki, Akishita, Masahiro, Nagata, Izumi, Kondo, Takahito
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Language:English
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Summary: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 γ-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 γ-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 γ-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.
ISSN:1071-5762
1029-2470
DOI:10.1080/10715760802566582