Methamphetamine and HIV-1 Tat down regulate β-catenin signaling: implications for methampetamine abuse and HIV-1 co-morbidity.
Methamphetamine and HIV-1 Tat down regulate β-catenin signaling: implications for methampetamine abuse and HIV-1 co-morbidity.
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DOI：
10.1007/s11481-011-9295-2
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发表时间：
2011-12
影响因子：
6.2
通讯作者：
Al-Harthi, Lena
中科院分区：
文献类型：
--
作者：
Sharma, Amit;Hu, Xiu-Ti;Napier, T. Celeste;Al-Harthi, Lena
甲基苯丙胺（Methe）滥用可加重HIV-1相关的神经认知障碍（HAND）。这种作用的潜在机制尚不完全清楚，但可能涉及甲基和HIV-1病毒毒素之间的合作，如转录的反式激活因子达特。HIV-1达特通过诱导包括星形胶质细胞增生在内的炎症过程介导CNS损伤。Wnt/β连环蛋白信号调节神经元和星形胶质细胞的存活过程。在此，我们评估了Meths对用达特转染的星形胶质细胞中Wnt/β-连环蛋白通路的影响。甲基和达特下调Wnt/β-连环蛋白信号传导> 50%，如在星形细胞瘤细胞系和原代人胎儿星形胶质细胞中通过TOP flash报告子活性所测量的。甲基苯丙胺和达特也下调LEF-1转录> 30%。LEF-1是β-catenin调控同源基因表达的关键伴侣。有趣的是，以细胞类型特异性方式诱导β-连环蛋白信号传导的雌激素在1.5和3 nM的生理浓度下使单独的Meth和达特对β-连环蛋白信号传导的作用正常化，但不是它们的组合作用。这些发现表明，Meth和达特可能发挥不同的机制来介导β-连环蛋白信号转导的下调。其后果可能导致CNS中HIV-1和Meth共病的病理生理效应。
Methamphetamine (Meth) abuse exacerbates HIV-1-associated neurocognitive disorders (HAND). The underlying mechanism for this effect is not entirely clear but likely involves cooperation between Meth and HIV-1 virotoxins, such as the transactivator of transcription, Tat. HIV-1 Tat mediates damage in the CNS by inducing inflammatory processes including astrogliosis. Wnt/β catenin signaling regulates survival processes for both neurons and astrocytes. Here, we evaluated the impact of Meth on the Wnt/β-catenin pathway in astrocytes transfected with Tat. Meth and Tat downregulated Wnt/β-catenin signaling by >50%, as measured by TOPflash reporter activity in both an astrocytoma cell line and primary human fetal astrocytes. Meth and Tat also down-regulated LEF-1 transcript by >30%. LEF-1 is a key partner of β-catenin to regulate cognate gene expression. Interestingly, estrogen, which induces β-catenin signaling in a cell-type specific manner, at physiological concentrations of 1.5 and 3 nM normalized individual Meth and Tat effects on β-catenin signaling but not their combined effects. These findings suggest that Meth and Tat likely exert different mechanisms to mediate down regulation of β-catenin signaling. The consequences of which may contribute to the pathophysiologic effects of HIV-1 and Meth co-morbidity in the CNS.
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影响因子：
3.2
作者：
Koutsilieri, E;Gotz, ME;Riederer, P
通讯作者：
Riederer, P
DOI：
10.1073/pnas.0611699104
发表时间：
2007-02-27
影响因子：
11.1
作者：
Eugenin, Eliseo A.;King, Jessie E.;Berman, Joan W.
通讯作者：
Berman, Joan W.
影响因子：
4.4
作者：
Hser, Yih-Ing;Evans, Elizabeth;Huang, David;Brecht, Mary-Lynn;Li, Libo
通讯作者：
Li, Libo
影响因子：
6
作者：
Kim, BO;Liu, Y;He, JJ
通讯作者：
He, JJ
影响因子：
6.2
作者：
Henderson, Lisa J.;Al-Harthi, Lena
通讯作者：
Al-Harthi, Lena