Jia Yichang, Zhou Jian, Tai Yilin, Wang Yizheng
Laboratory of Neural Signal Transduction, Institute of Neuroscience, Shanghai Institutes of Biological Sciences, Key Laboratory of Neurobiology, Shanghai 200031, China.
Nat Neurosci. 2007 May;10(5):559-67. doi: 10.1038/nn1870. Epub 2007 Apr 1.
Channels formed by the transient receptor potential (TRP) family of proteins have a variety of physiological functions. Here we report that two members of the TRP cation channel (TRPC) subfamily, TRPC3 and 6, protected cerebellar granule neurons (CGNs) against serum deprivation-induced cell death in cultures and promoted CGN survival in rat brain. In CGN cultures, blocking TRPC channels or downregulating TRPC3 or 6 suppressed brain-derived neurotrophic factor (BDNF)-mediated protection, BDNF-triggered intracellular Ca2+ elevation and BDNF-induced CREB activation. By contrast, overexpressing TRPC3 or 6 increased CREB-dependent reporter gene transcription and prevented apoptosis in the neurons deprived of serum, and this protection was blocked by the dominant negative form of CREB. Furthermore, downregulating TRPC3 or 6 induced CGN apoptosis in neonatal rat cerebellum, and this effect was rescued by overexpressing either TRPC3 or 6. Thus, our findings provide in vitro and in vivo evidence that TRPC channels are important in promoting neuronal survival.
由瞬时受体电位（TRP）蛋白家族形成的通道具有多种生理功能。在此我们报告，TRP阳离子通道（TRPC）亚家族的两个成员TRPC3和TRPC6，在培养物中可保护小脑颗粒神经元（CGN）免受血清剥夺诱导的细胞死亡，并在大鼠脑中促进CGN存活。在CGN培养物中，阻断TRPC通道或下调TRPC3或TRPC6会抑制脑源性神经营养因子（BDNF）介导的保护作用、BDNF触发的细胞内Ca2+升高以及BDNF诱导的CREB激活。相比之下，过表达TRPC3或TRPC6会增加CREB依赖的报告基因转录，并防止血清剥夺的神经元发生凋亡，且这种保护作用被CREB的显性负性形式所阻断。此外，下调TRPC3或TRPC6会诱导新生大鼠小脑的CGN凋亡，而过表达TRPC3或TRPC6可挽救这种效应。因此，我们的研究结果提供了体外和体内证据，表明TRPC通道在促进神经元存活中很重要。
