Neuroprotective activity of pDING in response to HIV-1 Tat.
Neuroprotective activity of pDING in response to HIV-1 Tat.
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DOI：
10.1002/jcp.24392
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发表时间：
2014-02
影响因子：
5.6
通讯作者：
Amini, Shohreh
中科院分区：
文献类型：
--
作者：
Darbinian, Nune;Khalili, Kamel;Amini, Shohreh
尽管神经元感染HIV-1的效率不高，但患有神经和神经认知障碍的艾滋病患者的大脑中经常会出现神经元损伤和死亡。显然，病毒蛋白包括TAT和由激活和/或感染的小胶质细胞、巨噬细胞和星形胶质细胞释放的细胞炎症因子导致神经细胞死亡。一些研究表明，HIV-1相关的神经细胞损伤是由信号通路的失调所介导的，这些信号通路部分地由一类丝氨酸/苏氨酸激酶控制。在这项研究中，我们证明了一种新的植物来源的磷酸结合蛋白pDING具有减轻HIV-1及其神经毒性Tat蛋白造成的损伤和死亡的能力。我们证明，pDING，也被称为p27SJ/p38SJ，可以保护细胞免受TAT诱导的神经元突起的丧失，并促进TAT介导的损伤后的神经元生长。此外，pDING的表达可以防止TAT诱导的氧化应激和线粒体通透性。PDING具有丰富的磷酸酶活性，控制着包括MAPK、CDK5及其下游靶蛋白MEF2在内的几种蛋白的活性，参与神经细胞保护。我们的结果表明，pDING在神经细胞中的表达减少了由TAT和其他神经毒剂引起的CDK5和MEF2的过度磷酸化水平，这些药物是由HIV-1感染的细胞分泌的。这些观察表明，pDING通过其磷酸酶活性，有能力操纵与HIV-1反应的神经细胞健康有关的几个因子的磷酸化状态和活性。
Although neurons are not productively infected with HIV-1, neuronal injury and death are frequently seen in the brains of AIDS patients with neurological and neurocognitive disorders. Evidently, viral proteins including Tat and cellular inflammatory factors released by activated and/or infected microglia, macrophages, and astrocytes contribute to neuronal cell death. Several studies have demonstrated that HIV-1 associated neuronal cell injury is mediated by dysregulation of signaling pathways that are controlled, in part, by a class of serine/threonine kinases. In this study we demonstrate that pDING, a novel plant-derived phosphate binding protein has the capacity to reduce the severity of injury and death caused by HIV-1 and its neurotoxic Tat protein. We demonstrate that pDING, also called p27SJ/p38SJ, protects cells from the loss of neuronal processes induced by Tat and promotes neuronal outgrowth after Tat-mediated injury. Further, expression of pDING prevents Tat-induced oxidative stress and mitochondrial permeability. With its profound phosphatase activity, pDING controls the activity of several kinases including MAPK, Cdk5 and their downstream target protein, MEF2, which is implicated in neuronal cell protection. Our results show that expression of pDING in neuronal cells diminishes the level of hyperphosphorylated forms of Cdk5 and MEF2 caused by Tat and the other neurotoxic agents that are secreted by the HIV-1 infected cells. These observations suggest that pDING, through its phosphatase activity, has the ability to manipulate the state of phosphorylation and activity of several factors involved in neuronal cell health in response to HIV-1.
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DOI：
10.1016/s1387-2656(05)11004-7
发表时间：
2005-01-01
期刊：
BIOTECHNOLOGY ANNUAL REVIEW, VOL 11
影响因子：
--
作者：
Berridge, MV;Herst, PM;Tan, AS
通讯作者：
Tan, AS
影响因子：
16.2
作者：
Flavell, Steven W.;Kim, Tae-Kyung;Gray, Jesse M.;Harmin, David A.;Hemberg, Martin;Hong, Elizabeth J.;Markenscoff-Papadimitriou, Eirene;Bear, Daniel M.;Greenberg, Michael E.
通讯作者：
Greenberg, Michael E.
通过细胞外信号调节的蛋白激酶5来调节神经元存活。
影响因子：
12.4
作者：
Finegan, K. G.;Wang, X.;Lee, E-J;Robinson, A. C.;Tournier, C.
通讯作者：
Tournier, C.
影响因子：
6.8
作者：
Braunewell KH;Dwary AD;Richter F;Trappe K;Zhao C;Giegling I;Schönrath K;Rujescu D
通讯作者：
Rujescu D
影响因子：
4.8
作者：
Gregoire, S;Tremblay, AM;Yang, XJ
通讯作者：
Yang, XJ