Methamphetamine causes differential regulation of Bcl2

Bcl-2是一种线粒体内膜蛋白，可抑制神经细胞凋亡。Bcl-2的表达通过减少活性氧的净细胞生成来抑制细胞死亡。不同研究者的研究提供了无可指责的证据，证明氧自由基在甲基苯丙胺（METH）诱导的神经毒性中的作用。此外，我们实验室的研究表明，过表达Bcl-2的永生化大鼠神经元细胞在体外可防止MET诱导的细胞凋亡。此外，安非他明可引起原代皮质细胞培养物中Bcl-X剪接变体表达的差异变化。这些观察结果表明，METH也可能导致Bcl-2相关基因的扰动时，管理啮齿动物。因此，本研究的目的是确定METH的使用是否确实与小鼠脑中Bcl-2相关基因表达的转录和翻译变化有关。在这里，我们报告说，METH的毒性方案确实导致促死亡Bcl-2家族基因BAD，BAX和BID的显着增加。与此同时，抗死亡基因Bcl-2和Bcl-XL显著降低。因此，这些结果支持了这样的观点，即注射毒性剂量的METH触发了哺乳动物大脑中程序性死亡途径的激活。

Bcl-2, an inner mitochondrial membrane protein, inhibits apoptotic neuronal cell death. Expression of Bcl-2 inhibits cell death by decreasing the net cellular generation of reactive oxygen species. Studies by different investigators have provided unimpeachable evidence of a role for oxygen-based free radicals in methamphetamine (METH) -induced neurotoxicity. In addition, studies from our laboratory have shown that immortalized rat neuronal cells that overexpress Bcl-2 are protected against METH-induced apoptosis in vitro. Moreover, the amphetamines can cause differential changes in the expression of Bcl-X splice variants in primary cortical cell cultures. These observations suggested that METH might also cause perturbations of Bcl-2-related genes when administered to rodents. Thus, the present study was conducted to determine whether the use of METH might indeed be associated with transcriptional and translational changes in the expression of Bcl-2-related genes in the mouse brain. Here we report that a toxic regimen of METH did cause significant increases in the pro-death Bcl-2 family genes BAD, BAX, and BID. Concomitantly, there were significant decreases in the anti-death genes Bcl-2 and Bcl-XL. These results thus support the notion that injections of toxic doses of METH trigger the activation of the programmed death pathway in the mammalian brain.