House Shirley B, Rusnak Milan, Liu Xiu-Huai, Youle Richard J, Gainer Harold
Laboratory of Neurochemistry, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Exp Neurol. 2006 Jul;200(1):267-71. doi: 10.1016/j.expneurol.2006.02.009. Epub 2006 Apr 19.
Hypothalamic magnocellular neurons (MCNs) are highly vulnerable to axotomy-induced cell death in vivo and in vitro. In this study, we determined whether the anti-apoptotic agent Bcl-xL, a member of the Bcl-2 family which prevents programmed cell death in the central nervous system, can rescue oxytocin (OT) and vasopressin (VP) MCNs in the supraoptic nucleus (SON) in organotypic culture. We found that the novel, membrane permeant form of Bcl-xL that we employed in these studies protected both OT and VP MCNs from degeneration as long as the Bcl-xL was present in the medium. In contrast, z-VAD-fmk, an inhibitor of caspases that are involved in apoptosis, was less effective in that it significantly rescued OT MCNs (P < 0.01) but not VP MCNs (P > 0.09). Unlike the Bcl-xL, Z-VAD-fmk's effectiveness in reducing MCN cell death was not sustained for the full 15 days in vitro.
下丘脑大细胞神经元（MCNs）在体内和体外都极易因轴突切断而发生细胞死亡。在本研究中，我们确定了抗凋亡剂Bcl-xL（一种Bcl-2家族成员，可防止中枢神经系统中的程序性细胞死亡）是否能挽救器官型培养中视上核（SON）的催产素（OT）和加压素（VP）MCNs。我们发现，我们在这些研究中使用的新型膜渗透性Bcl-xL形式只要存在于培养基中，就能保护OT和VP MCNs不发生退化。相比之下，z-VAD-fmk（一种参与凋亡的半胱天冬酶抑制剂）效果较差，因为它能显著挽救OT MCNs（P < 0.01），但不能挽救VP MCNs（P > 0.09）。与Bcl-xL不同，Z-VAD-fmk在减少MCN细胞死亡方面的有效性在体外15天内并未持续。
