Middleton G, Nunez G, Davies A M
School of Biological and Medical Sciences, University of St. Andrews, Scotland.
Development. 1996 Feb;122(2):695-701. doi: 10.1242/dev.122.2.695.
Bcl-2, Bcl-x and Bax are members fo a family of cytoplasmic proteins that influence cell survival. Whereas increased expression of Bcl-2 or Bcl-x promotes cell survival following withdrawal of survival factors, increased expression of Bax is thought to suppress survival. To investigate the potential roles of these proteins in regulating the survival of developing neurons, we compared the effects of overexpressing these proteins in embryonic neurons deprived of different neurotrophic factors in vitro. Surprisingly, overexpression of Bax rescued populations of sensory neurons deprived of nerve growth factor, as did overexpression of Bcl-2 and two Bcl-x variants, Bcl-XL and Bcl-Xbeta. Bax also enhanced the survival of ciliary neurons deprived of ciliary neurotrophic factor, although this effect was short-lived. Whereas Bcl-2 overexpression did not affect the survival response of neurons to neurotrophic factors, Bax overexpression partially inhibited the action of neurotrophic factors. Co-injection of Bcl-2 and Bax expression vectors promoted the survival of neurotrophic factor-deprived neurons if either was in excess, but failed to rescue neurons if they injected at a 1:1 ratio. Our findings demonstrate that Bax can promote the survival of neurotrophic factor-deprived neurons and that its effect on survival is dominant to that of neurotrophic factors. Our results also argue that the relative amounts of Bcl-2 and Bax are critical in regulating neuronal survival.
Bcl-2、Bcl-x和Bax是影响细胞存活的一类细胞质蛋白家族的成员。虽然Bcl-2或Bcl-x表达增加可促进在去除存活因子后细胞的存活，但Bax表达增加被认为会抑制存活。为了研究这些蛋白在调节发育中神经元存活方面的潜在作用，我们比较了在体外缺乏不同神经营养因子的胚胎神经元中过表达这些蛋白的效果。令人惊讶的是，Bax的过表达挽救了缺乏神经生长因子的感觉神经元群体，Bcl-2以及两种Bcl-x变体Bcl-XL和Bcl-Xbeta的过表达也有同样效果。Bax还增强了缺乏睫状神经营养因子的睫状神经元的存活，尽管这种效果是短暂的。虽然Bcl-2的过表达不影响神经元对神经营养因子的存活反应，但Bax的过表达部分抑制了神经营养因子的作用。如果Bcl-2和Bax表达载体中的任何一种过量，共注射可促进缺乏神经营养因子的神经元的存活，但以1:1比例注射则无法挽救神经元。我们的研究结果表明，Bax可以促进缺乏神经营养因子的神经元的存活，并且其对存活的影响比神经营养因子的影响更具主导性。我们的结果还表明，Bcl-2和Bax的相对量在调节神经元存活中至关重要。
