Inhibition of tumor necrosis factor-alpha signaling prevents human immunodeficiency virus-1 protein Tat and methamphetamine interaction.
Inhibition of tumor necrosis factor-alpha signaling prevents human immunodeficiency virus-1 protein Tat and methamphetamine interaction.
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抑制肿瘤坏死因子-α 信号传导可防止人类免疫缺陷病毒 1 蛋白 Tat 与甲基苯丙胺相互作用。
DOI：
10.1016/j.nbd.2006.05.005
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发表时间：
2006
影响因子：
6.1
通讯作者：
Maragos,WilliamF
中科院分区：
文献类型：
--
作者：
Theodore,Shaji;Cass,WayneA;Nath,Avindra;Steiner,Joseph;Young,Kristie;Maragos,WilliamF
我们以前的研究表明，精神刺激剂甲基苯丙胺(MA)和人类免疫缺陷病毒-1(HIV-1)蛋白TAT相互作用，导致多巴胺能神经毒性增加。本研究探讨了肿瘤坏死因子-α是否介导了TAT和MA之间的相互作用。在SPRAGUE-DAWLEY大鼠中，注射TAT引起纹状体肿瘤坏死因子-α水平的轻微但显著的增加，而MA没有引起变化。TAT+TMA诱导的肿瘤坏死因子-α升高与单独TAT无明显差异。对肿瘤坏死因子-α水平的时间分析显示，服用TAT后4小时，肿瘤坏死因子-DNA水平增加了50倍。在C57BL/6小鼠中，TAT+TMA诱导纹状体多巴胺水平下降50%，在缺乏这两种肿瘤坏死因子-α受体的小鼠中，这种下降明显减弱。肿瘤坏死因子-α合成抑制剂显著减轻海马神经元培养中TAT+MMA的神经毒性。结果提示，TAT诱导的肿瘤坏死因子-α的升高可能使多巴胺能终末易于受到MA的继发性损害。
Our previous studies demonstrated that the psychostimulant methamphetamine (MA) and the human immunodeficiency virus-1 (HIV-1) protein Tat interacted to cause enhanced dopaminergic neurotoxicity. The present study examined whether tumor necrosis factor-alpha (TNF-α) mediates the interaction between Tat and MA. In Sprague–Dawley rats, injections of Tat caused a small but significant increase in striatal TNF-α level, whereas MA resulted in no change. The increase in TNF-α induced by Tat + MA was not significantly different from that induced by Tat alone. Temporal analysis of TNF-α levels revealed a 50-fold increase 4 h after Tat administration. In C57BL/6 mice, Tat + MA induced a 50% decline in striatal dopamine levels, which was significantly attenuated in mice lacking both receptors for TNF-α. TNF-α synthesis inhibitors significantly attenuated Tat + MA neurotoxicity in hippocampal neuronal culture. The results suggest that Tat-induced elevation of TNF-α may predispose the dopaminergic terminals to subsequent damage by MA.