Poly(ADP-ribose) polymerase - The nuclear target in signal transduction and its role in brain ischemia-reperfusion injury
Poly(ADP-ribose) polymerase - The nuclear target in signal transduction and its role in brain ischemia-reperfusion injury
复制标题
信号转导的核靶向聚腺苷二磷酸核糖聚合酶及其在脑缺血再灌注损伤中的作用
DOI：
10.1385/mn:31:1-3:149
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发表时间：
2005-01-01
影响因子：
5.1
通讯作者：
Zambrzycka, A
中科院分区：
文献类型：
--
作者：
Strosznajder, RP;Jesko, H;Zambrzycka, A
聚（ADP-核糖）聚合酶（Poly（ADP-ribose）polymerase，PARP）-1是一种DNA缺口传感器，其将ADP-核糖从聚合物形式的β NAD（+）转化为超过40种核蛋白，特别是组蛋白、几种转录因子和PARP本身，调节它们的活性和功能。DNA断裂激活的PARP-1促进转录、复制和DNA碱基切除修复。最近的研究表明，PARP-1是细胞膜上由去极化和胆碱能和多巴胺能受体刺激诱发的快速信号的新的核靶点。氧化应激过程中过氧硝酸盐诱导的DNA损伤过度激活PARP-1可导致缺血再灌注损伤、炎症和糖尿病后NAD（+）/ATP耗竭导致细胞死亡。PARP-1通过与核因子-κ β、p53等转录因子的相互作用，可能显著调节细胞的存活和死亡，是一种死亡途径。PARP-1的药理学调节可能为神经保护提供一种新的有效途径。
Poly(ADP-ribose) polymerase (PARP)-l is a DNA nick sensor that transforms ADP-ribose from beta NAD(+) in the form of polymer to over 40 nuclear proteins, particularly to histones, several transcription factors, and PARP itself, modulating their activities and functions. PARP-1 activated by DNA breaks facilitates transcription, replication, and DNA base excision repair. The last studies indicate that PARP-1 is the new nuclear target for fast signals evoked in cell membranes by depolarization and cholinergic and glutaminergic receptors stimulation. Excessive activation of PARP-1 by peroxynitrate-evoked DNA damage during oxidative stress can cause cell death by NAD(+)/ATP depletion after ischemia-reperfusion injury, inflammation, and diabetes mellitus. The PARP-1 through interaction with nuclear factor-kappa beta, p53, and other transcription factors might significantly modulate cell survival and death and a type of death pathway. The pharmacological modulation of PARP-1 might offer a new effective approach for neuroprotection.