Batistatou A, Merry D E, Korsmeyer S J, Greene L A
Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, New York 10032.
J Neurosci. 1993 Oct;13(10):4422-8. doi: 10.1523/JNEUROSCI.13-10-04422.1993.
Past studies have shown that serum-free cultures of PC12 cells are a useful model system for studying the mechanisms of neuronal death after neurotrophic factor deprivation. These cultures, as well as NGF-deprived cultures of sympathetic neurons, manifest and endonuclease activity that leads to "apoptotic" internucleosomal DNA cleavage. Overexpression of the proto-oncogene bcl-2 blocks apoptotic death in various cell types. To study the actions of this protein in neuronal cells, we derived PC12 cell lines stably transfected with a cDNA encoding human bcl-2. It is reported here that lines expressing high levels of the exogenous bcl-2 protein are protected from both death and apoptotic DNA fragmentation caused by removal of trophic support. However, expression of high levels of exogenous bcl-2 neither mimics nor interferes with promotion of neurite outgrowth by NGF.
以往的研究表明，PC12细胞的无血清培养是研究神经营养因子剥夺后神经元死亡机制的有用模型系统。这些培养物以及交感神经元的NGF剥夺培养物表现出一种内切核酸酶活性，该活性导致“凋亡性”核小体间DNA裂解。原癌基因bcl-2的过表达可阻止多种细胞类型的凋亡性死亡。为了研究该蛋白在神经元细胞中的作用，我们构建了稳定转染编码人bcl-2的cDNA的PC12细胞系。本文报道，表达高水平外源性bcl-2蛋白的细胞系可免受因营养支持撤除导致的死亡和凋亡性DNA片段化。然而，高水平外源性bcl-2的表达既不模拟也不干扰NGF对神经突生长的促进作用。
