Bax promotes neuronal survival and antagonises the survival effects of neurotrophic factors.
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.
Middleton
G
G
School of Biological and Medical Sciences, University of St. Andrews, Scotland.
Nunez
G
G
Davies
A M
AM
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D020934:Ciliary Neurotrophic Factor; D019204:GTP-Binding Proteins / Q000502:physiology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology; D007700:Kinetics; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D013997:Time Factors; D012668:Trigeminal Ganglion / Q000166:cytology / Q000196:embryology; D051028:bcl-2-Associated X Protein
D020934:Ciliary Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019204:GTP-Binding Proteins