l-Selegiline Potentiates the Cellular Poly(ADP-Ribosyl)ation Response to Ionizing Radiation
l-Selegiline Potentiates the Cellular Poly(ADP-Ribosyl)ation Response to Ionizing Radiation
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l-司来吉兰增强细胞对电离辐射的聚（ADP-核糖基）化反应
DOI：
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发表时间：
2003
影响因子：
3.5
通讯作者：
A. Bürkle
中科院分区：
文献类型：
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作者：
C. Brabeck;R. Pfeiffer;A. Leake;S. Beneke;Ralph G Meyer;A. Bürkle
由烷化剂、氧化剂或电离辐射诱导的DNA链断裂触发核蛋白与聚（ADP-核糖）的共价修饰，其大部分由聚（ADP-核糖）聚合酶-1催化，并在DNA碱基切除修复中起作用。单核血细胞的聚（ADP-核糖基）化能力与哺乳动物物种的寿命呈正相关。在这里，我们表明，l-司来吉兰，一种抗帕金森病药物，具有神经保护活性和延长实验动物寿命的作用，可以加强γ-辐射诱导的聚（ADP-核糖）在完整细胞中的形成。将COR 4仓鼠细胞与l-司来吉兰（50 nM）孵育不同的时间段，然后进行γ-照射（45戈伊）。定量细胞聚（ADP-核糖）水平在10分钟后开始照射显示显着增加（高达1.8倍），在细胞预孵育的药物为8小时至7天相比，无药物照射的控制。司来吉兰诱导的未照射细胞的聚（ADP-核糖）水平没有变化，也没有基础或辐射诱导的DNA链断裂。令人惊讶的是，聚（ADP-核糖）聚合酶-1蛋白下调的l-司来吉兰治疗。添加l-司来吉兰纯化的聚（ADP-核糖）聚合酶-1没有改变酶的活性。总之，本研究的结果确定了一种新的干预，以加强细胞的聚（ADP-核糖基）化反应。我们推测，l-司来吉兰的作用是由于调节辅助蛋白调节聚（ADP-核糖）聚合酶-1的活性和细胞的聚（ADP-核糖基）化能力的增加可能有助于神经保护潜力和/或寿命延长所提供的l-司来吉兰。
DNA strand breaks induced by alkylating agents, oxidants, or ionizing radiation trigger the covalent modification of nuclear proteins with poly(ADP-ribose), which is catalyzed for the most part by poly(ADP-ribose) polymerase-1 and plays a role in DNA base-excision repair. Poly(ADP-ribosyl)ation capacity of mononuclear blood cells correlates positively with life span of mammalian species. Here, we show that l-selegiline, an anti-Parkinson drug with neuroprotective activity and life span-extending effect in laboratory animals, can potentiate γ-radiation-induced poly(ADP-ribose) formation in intact cells. COR4 hamster cells were incubated with l-selegiline (50 nM) for various time periods, followed by γ-irradiation (45 Gy). Quantification of cellular poly(ADP-ribose) levels at 10 min after starting the irradiation revealed significant increases (up to 1.8-fold) in cells preincubated with the drug for 8 h to 7 days compared with drug-free irradiated controls. There was no selegiline-induced change in poly(ADP-ribose) levels of unirradiated cells nor in basal or radiation-induced DNA strand breaks, respectively. Surprisingly, poly(ADP-ribose) polymerase-1 protein was down-regulated by l-selegiline treatment. Addition of l-selegiline to purified poly(ADP-ribose) polymerase-1 did not alter enzymatic activity. In conclusion, the results of the present study identify a novel intervention to potentiate the cellular poly(ADP-ribosyl)ation response. We hypothesize that the effect of l-selegiline is due to modulation of accessory proteins regulating poly(ADP-ribose) polymerase-1 activity and that increased cellular poly- (ADP-ribosyl)ation capacity may contribute to the neuroprotective potential and/or life span extension afforded by l-selegiline.
短暂性整体缺血和红藻氨酸对沙鼠和大鼠大脑中聚（ADP-核糖）聚合酶（PARP）基因表达和蛋白水解裂解的影响。
DOI：
10.1016/s0169-328x(00)00122-4
发表时间：
2000
期刊：
Brain research. Molecular brain research
影响因子：
--
作者：
Liu,J;Ying,W;Massa,S;Duriez,PJ;Swanson,RA;Poirier,GG;Sharp,FR
通讯作者：
Sharp,FR