Can radiation-induced apoptosis be modulated by inhibitors of energy metabolism?
Can radiation-induced apoptosis be modulated by inhibitors of energy metabolism?
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DOI：
10.1080/09553000601121157
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发表时间：
2007-02-01
影响因子：
2.6
通讯作者：
Renan, M. J.
中科院分区：
文献类型：
--
作者：
Hunter, A. J.;Hendrikse, A. S.;Renan, M. J.
目的：为了确定能量代谢的抑制剂，2-脱氧葡萄糖（2DG）和叠氮化钠，对辐射诱导的apoptosis.Materials和方法：辐射诱导的细胞凋亡的U937单核细胞白血病细胞暴露于能量抑制剂照射后确定。使用形态学标准对细胞凋亡进行显微镜评分。通过评估葡萄糖消耗和乳酸产生来确定糖酵解。在酶促转化为ATP后，使用荧光素酶测定法测量腺嘌呤核苷酸水平。呼吸测定使用克拉克型oxygen electrode.Results：除了他们的凋亡诱导性能，2DG和叠氮化物修饰辐射后细胞凋亡。2DG诱导细胞凋亡放射增敏后暴露于较低浓度（5 mM，10 mM）照射后20小时，而5小时暴露于较高剂量高达100 mM的辐射保护水平被发现。相比之下，所有剂量的叠氮化物检查（5 - 50 mM）诱导细胞凋亡的辐射保护在所有时间检查。随着2DG剂量的增加，糖酵解通量和ATP水平迅速下降，但能荷保持不变。糖酵解受叠氮化物的影响较小，暴露后ATP水平最初保持不变，但在照射后3小时以剂量依赖性方式降低。然而，能量电荷是不受叠氮化物在浓度examined.Conclusions：2DG和叠氮化物可以影响辐射诱导的细胞凋亡可能通过影响糖酵解和ATP水平。我们认为，能量代谢的调制提供了辐射诱导的细胞凋亡途径的机制的见解。
Purpose: To determine the effect of the inhibitors of energy metabolism, 2-deoxyglucose (2DG) and sodium azide, on radiation-induced apoptosis.Materials and methods: Radiation-induced apoptosis was determined in U937 monocytic leukaemia cells exposed to energy inhibitors post-irradiation. Apoptosis was scored microscopically using morphological criteria. Glycolysis was determined by assessing glucose consumption and lactate production. Adenine nucleotide levels were measured using a luciferase assay after enzymatic conversion to ATP. Respiration was measured using a Clark-type oxygen electrode.Results: In addition to their apoptosis-inducing properties, both 2DG and azide modified post-irradiation apoptosis. 2DG induced apoptotic radiosensitization after exposure to lower concentrations (5 mM, 10 mM) up to 20 h post-irradiation while a level of radioprotection was found after 5 h exposure to higher doses up to 100 mM. By contrast, all doses of azide examined (5 - 50 mM) induced apoptotic radioprotection at all times examined. Glycolytic flux and ATP levels fell rapidly with increasing 2DG dose but energy charge remained unchanged. Glycolysis was less influenced by azide, with ATP levels being initially maintained after exposure but decreasing in a dose-dependent manner at 3 h post-irradiation. However, energy charge was unaffected by azide at the concentrations examined.Conclusions: Both 2DG and azide can influence radiation-induced apoptosis possibly through their effects on glycolysis and ATP levels. We suggest that modulation of energy metabolism provides mechanistic insight into radiation-induced apoptotic pathways.