Sigma-1 receptor agonists provide neuroprotection against gp120 via a change in bcl-2 expression in mouse neuronal cultures
Sigma-1 receptor agonists provide neuroprotection against gp120 via a change in bcl-2 expression in mouse neuronal cultures
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Sigma-1 受体激动剂通过改变小鼠神经元培养物中 bcl-2 的表达来提供针对 gp120 的神经保护
DOI：
10.1016/j.brainres.2011.10.053
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发表时间：
2012-01
期刊：
影响因子：
2.9
通讯作者：
陈德喜
中科院分区：
文献类型：
--
作者：
陈德喜
虽然联合抗逆转录病毒治疗显著改善了HIV-1感染患者的预后，降低了HIV-1相关痴呆的发病率，但这种疾病的累积患病率，特别是轻度或无症状的神经认知障碍，并没有减少。因此，除了积极的抗逆转录病毒治疗，寻找有效的神经保护方法是非常重要的。σ-1受体广泛分布于中枢神经系统。σ-1受体激动剂在体内和体外研究中在许多神经病变和神经毒性中具有强大的神经保护作用。本研究旨在探讨sigma-1受体激动剂4-苯基-1-（4-苯基丁基）哌啶（PPBP）对HIV-1蛋白gp 120的神经保护作用。将原代皮层神经元培养物暴露于不同浓度的gp 120;为了研究sigma-1受体激动剂的神经保护作用，在存在或不存在预孵育的sigma-1受体拮抗剂rimcazole（5μM）的情况下，用PPBP（10μM）预处理细胞。采用钙黄绿素/PI摄取试验、乳酸脱氢酶（LDH）漏出试验或TUNEL法检测细胞凋亡，采用MAP-2免疫荧光染色的形态计量学方法检测神经突变性。实时定量PCR和Western blot检测凋亡相关基因bax和bcl-2的mRNA和蛋白水平。结果表明，gp 120可诱导神经元凋亡和轴突变性，且呈浓度依赖性，PPBP可减轻gp 120的神经毒性。同时，gp 120可诱导bcl-2和bax的低表达，PPBP仅能逆转bcl-2的低表达。目前的数据表明，PPBP，至少，部分保护神经元对gp 120通过调节bcl-2的表达。
Although combined antiretroviral therapy has significantly improved the prognosis of HIV-1 infected patients and decreased the incidence of HIV-1 associated dementia, the cumulative prevalence of this disease, in particular, mild or asymptomatic neurocognitive impairment, has not decreased. Thus, in addition to active antiretroviral therapy, the search for an effective neuroprotective approach is very important. Sigma-1 receptors are widely distributed in the central nervous system. Sigma-1 receptor agonists are robustly neuroprotective in many neuropathy and neurotoxicity in vivo and in vitro studies. This study aims to investigate possible neuroprotective effects of sigma-1 receptor agonist, 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) against HIV-1 protein gp120. Primary cortical neuronal cultures were exposed to gp120 in different concentrations; to investigate neuroprotective effects of sigma-1 receptor agonist, cells were pre-treated with PPBP (10μM) in the presence or absence of pre-incubated sigma-1 receptor antagonist rimcazole (5μM). Cell apoptosis was confirmed with calcein/PI uptake test, lactate dehydrogenase (LDH) leakage assay or TUNEL assay and neurite degeneration was evaluated with morphometry via MAP-2 stained immunofluorescence. The mRNA and protein levels of apoptosis associated bax and bcl-2 were determined with real-time qPCR and Western blot. The results showed that gp120 could induce neuronal apoptosis and neurite degeneration in a concentration dependent manner and PPBP could attenuate the neurotoxicity of gp120. Simultaneously, gp120 could induce low expression of bcl-2 and bax, but only low expression of bcl-2 could be reversed by PPBP. The present data suggest that PPBP, at least, in part protects the neuron against gp120 by regulating bcl-2 expression.
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影响因子：
4.4
作者：
K. Tchedre;T. Yorio
通讯作者：
K. Tchedre;T. Yorio
影响因子：
0.6
作者：
Z. Fišar;J. Hroudová
通讯作者：
Z. Fišar;J. Hroudová
影响因子：
3.7
作者：
Zhuying Wang;O. Pekarskaya;M. Bencheikh;W. Chao;H. Gelbard;A. Ghorpade;J. Rothstein;D. Volsky
通讯作者：
Zhuying Wang;O. Pekarskaya;M. Bencheikh;W. Chao;H. Gelbard;A. Ghorpade;J. Rothstein;D. Volsky
DOI：
10.1196/annals.1403.010
发表时间：
2007-01-01
期刊：
NEUROPROTECTIVE AGENTS: EIGHTH INTERNATIONAL NEUROPROTECTION SOCIETY MEETING
影响因子：
--
作者：
Mocchetti, Italo;Nosheny, Rachel L.;Meyer, Edwin M.
通讯作者：
Meyer, Edwin M.
影响因子：
2.5
作者：
FRENCH, ED;CECI, A
通讯作者：
CECI, A