Krieglstein K, Suter-Crazzolara C, Fischer W H, Unsicker K
Department of Anatomy and Cell Biology, University of Heidelberg, Germany.
EMBO J. 1995 Feb 15;14(4):736-42. doi: 10.1002/j.1460-2075.1995.tb07052.x.
The superfamily of transforming growth factors-beta (TGF-beta) comprises an expanding list of multifunctional proteins serving as regulators of cell proliferation and differentiation. Prominent members of this family include the TGF-beta s 1-5, activins, bone morphogenetic proteins and a recently discovered glial cell line-derived neurotrophic factor (GDNF). In the present study we demonstrate and compare the survival promoting and neuroprotective effects of TGF-beta 1, -2 and -3, activin A and GDNF for midbrain dopaminergic neurons in vitro. All proteins increase the survival of tyrosine hydroxylase-immunoreactive dopaminergic neurons isolated from the embryonic day (E) 14 rat mesencephalon floor to varying extents (TGF-beta s 2.5-fold, activin A and GDNF 1.6-fold). TGF-beta s, activin A and GDNF did not augment numbers of very rarely observed astroglial cells visualized by using antibodies to glial fibrillary acidic protein and had no effect on cell proliferation monitored by incorporation of BrdU. TGF-beta 1 and activin A protected dopaminergic neurons against N-methyl-4-phenylpiridinium ion toxicity. Reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated that TGF-beta 2 mRNA, but not GDNF mRNA, is expressed in the E14 rat midbrain floor and in mesencephalic cultures. We conclude that TGF-beta s 1-3, activin A and GDNF share a neurotrophic capacity for developing dopaminergic neurons, which is not mediated by astroglial cells and not accompanied by an increase in cell proliferation.
转化生长因子-β(TGF-β)超家族包含越来越多的多功能蛋白质,这些蛋白质作为细胞增殖和分化的调节因子。该家族的主要成员包括TGF-β 1-5、激活素、骨形态发生蛋白以及最近发现的胶质细胞系源性神经营养因子(GDNF)。在本研究中,我们展示并比较了TGF-β 1、-2和-3、激活素A以及GDNF对体外中脑多巴胺能神经元的存活促进和神经保护作用。所有蛋白质都不同程度地提高了从胚胎第14天(E14)大鼠中脑腹侧分离的酪氨酸羟化酶免疫反应性多巴胺能神经元的存活率(TGF-β为2.5倍,激活素A和GDNF为1.6倍)。TGF-β、激活素A和GDNF并未增加使用胶质纤维酸性蛋白抗体观察到的极少见的星形胶质细胞数量,并且对通过掺入BrdU监测的细胞增殖没有影响。TGF-β 1和激活素A保护多巴胺能神经元免受N-甲基-4-苯基吡啶离子毒性的影响。逆转录-聚合酶链反应(RT-PCR)分析表明,TGF-β 2 mRNA在E14大鼠中脑腹侧和中脑培养物中表达,但GDNF mRNA未表达。我们得出结论,TGF-β 1-3、激活素A和GDNF对发育中的多巴胺能神经元具有神经营养能力,这种能力不是由星形胶质细胞介导的,也不会伴随着细胞增殖的增加。