Protective effects of transduced Tat-DJ-1 protein against oxidative stress and ischemic brain injury.
Protective effects of transduced Tat-DJ-1 protein against oxidative stress and ischemic brain injury.
复制标题
DOI：
10.3858/emm.2012.44.10.067
复制
发表时间：
2012-10-31
影响因子：
12.8
通讯作者：
Choi SY
中科院分区：
文献类型：
--
作者：
Jeong HJ;Kim DW;Kim MJ;Woo SJ;Kim HR;Kim SM;Jo HS;Hwang HS;Kim DS;Cho SW;Won MH;Han KH;Park JS;Eum WS;Choi SY
活性氧（ROS）有助于发展的许多神经元疾病，包括缺血。DJ-1，也称为PARK 7，在转录调控中起重要作用，作为分子伴侣和抗氧化剂。在本研究中，我们研究了DJ-1蛋白是否对体外氧化应激诱导的神经元细胞死亡和体内缺血动物模型具有保护作用。为了探索DJ-1蛋白在保护缺血性细胞死亡中的潜在作用，我们构建了细胞可渗透的Tat-DJ-1融合蛋白。Tat-DJ-1蛋白以剂量和时间依赖性方式有效地转导到神经元细胞中。转导的Tat-DJ-1蛋白增加了细胞对过氧化氢（H2 O2）毒性的存活率，也减少了细胞内的ROS。此外，Tat-DJ-1蛋白抑制H2 O2诱导的DNA断裂。此外，在动物模型中，免疫组织化学分析显示，Tat-DJ-1蛋白防止海马CA 1区短暂前脑缺血诱导的神经元细胞死亡。这些结果表明，转导的Tat-DJ-1蛋白在体外和体内保护细胞免于死亡，表明Tat-DJ-1的转导可用作与氧化应激相关的缺血性损伤的治疗剂。
Reactive oxygen species (ROS) contribute to the development of a number of neuronal diseases including ischemia. DJ-1, also known to PARK7, plays an important role in transcriptional regulation, acting as molecular chaperone and antioxidant. In the present study, we investigated whether DJ-1 protein shows a protective effect against oxidative stress-induced neuronal cell death in vitro and in ischemic animal models in vivo. To explore DJ-1 protein's potential role in protecting against ischemic cell death, we constructed cell permeable Tat-DJ-1 fusion proteins. Tat-DJ-1 protein efficiently transduced into neuronal cells in a dose- and time-dependent manner. Transduced Tat-DJ-1 protein increased cell survival against hydrogen peroxide (H2O2) toxicity and also reduced intracellular ROS. In addition, Tat-DJ-1 protein inhibited DNA fragmentation induced by H2O2. Furthermore, in animal models, immunohistochemical analysis revealed that Tat-DJ-1 protein prevented neuronal cell death induced by transient forebrain ischemia in the CA1 region of the hippocampus. These results demonstrate that transduced Tat-DJ-1 protein protects against cell death in vitro and in vivo, suggesting that the transduction of Tat-DJ-1 may be useful as a therapeutic agent for ischemic injuries related to oxidative stress.
登录
查看更多内容
影响因子：
10.7
作者：
Lucas, J. Ignasi;Marin, Ignacio
通讯作者：
Marin, Ignacio
影响因子：
56.9
作者：
Bonifati, V;Rizzu, P;Heutink, P
通讯作者：
Heutink, P
影响因子：
5.6
作者：
Zhou, WB;Zhu, M;Fink, AL
通讯作者：
Fink, AL
影响因子：
2
作者：
Alexandrova, M;Bochev, P;Simeonova, V
通讯作者：
Simeonova, V
影响因子：
7.4
作者：
Eum, WS;Kim, DW;Choi, SY
通讯作者：
Choi, SY