标题：Cellular NAD depletion and decline of SIRT1 activity play critical roles in PARP-1-mediated acute epileptic neuronal death in vitro
作者：Wang, Shengjun; Yang, Xue; Lin, Youting; Qiu, Xiaoxue; Li, Hui; Zhao, Xiuhe; Cao, Lili; Liu, Xuewu; Pang, Yuejiu; Wang, Xuping; Ch 更多 作者机构：[Wang, Shengjun; Yang, Xue; Qiu, Xiaoxue; Zhao, Xiuhe; Cao, Lili; Liu, Xuewu; Chi, Zhaofu] Shandong Univ, Qilu Hosp, Dept Neurol, Jinan 250100, People 更多
通讯作者地址：[Chi, ZF]Shandong Univ, Qilu Hosp, Dept Neurol, 107 Wenhua Xi Rd, Jinan 250100, Peoples R China.
关键词：Poly(ADP-ribose)polymerase-1; NAD; Apoptosis-inducing factor; SIRT1;; Epilepsy; Neuronal death
摘要：Intense poly(ADP-ribose) polymerase-1 (PARP-1) activation was implicated as a major cause of caspase-independent cell death in the hippocampal neuronal culture (HNC) model of acute acquired epilepsy (AE). The molecular mechanisms are quite complicated. The linkage among neuronal death, cellular nicotinamide, adenine dinucleotide (NAD) levels, apoptosis-inducing factor (AIF) translocation, SIRT1 expression and activity were investigated here. The results showed that PARP-1 over-activation caused by Me-free stimuli led to cellular NAD depletion which could block AIF translocation from mitochondria to nucleus and attenuate neuronal death. Also, SIRT1 deacetylase activity was reduced by Mg2+-free treatment, accompanied by elevated ratio of neuronal death, which could be rescued by NAD repletion. These data demonstrated that cellular NAD depletion and decline of SIRT1 activity play critical roles in PARP-1-mediated epileptic neuronal death in the HNC model of acute AE. (C) 2013 Elsevier B.V. All rights reserved.