Radioresistance of human carcinoma cells is correlated to a defect in raft membrane clustering
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- 作者：Clara Bionda ; Elie Hadchity ; Gersende Alphonse ; Olivier Chapet ; Robert Rousson ; Claire Rodriguez-Lafrasse ; Dominique Ardail
- 关键词：Gamma irradiation ; Ceramide ; Radioresistant squamous carcinoma cells ; Reactive oxygen species ; Lipid rafts ; Acid sphingomyelinase
- 刊名：Free Radical Biology and Medicine
- 出版年：2007
- 出版时间：1 September 2007
- 年：2007
- 卷：43
- 期：5
- 页码：681-694
- 全文大小：1081 K
文摘
In addition to DNA damage, exposure to irradiation involves the plasma membrane in the early phases of γ-ray-induced cell death. The involvement of raft microdomains following γ-radiation derives essentially from the role of ceramide as a critical component leading to apoptosis. It is demonstrated here that γ-irradiation of a radiosensitive human head and neck squamous carcinoma cell line (SCC61) results in the triggering of raft coalescence to larger membrane platforms associated with the externalization of an acid sphingomyelinase (A-SMase), leading to ceramide release in raft, 30 min postirradiation. For the first time, we show that this structural rearrangement is defective in the radioresistant SQ20B cells and associated with the lack of A-SMase activation and translocation, a result which could explain in part their resistance to apoptosis following ionizing radiation. Moreover, we show that SQ20B are protected against radiation injury through a fivefold upper level of endogenous glutathione compared to SCC61. Overcoming the endogenous antioxidant defenses of SQ20B through either H2O2 treatment or GSH depletion triggers A-SMase activation and translocation, raft coalescence, and apoptosis. On the contrary, ROS scavengers abolished these events in radiosensitive SCC61 cells. Translation of this concept to tumor biology suggests that manipulation of rafts through redox equilibrium may provide opportunities for radiosensitization of tumor cells.