Role of Bcl-2 in the brain-derived neurotrophic factor survival response.
Developing neurons die if they fail to obtain an adequate supply of neurotrophins from their targets but how neurotrophins suppress cell death is not known. Although over-expression of exogenous Bcl-2 can prevent the death of cultured neurons deprived of members of the nerve growth factor family of neurotrophins it is not known if this effect is physiologically relevant. To determine if Bcl-2 participates in the neurotrophin survival response we used antisense bcl-2 RNA to inhibit endogenous Bcl-2 expression. Here we show that brain-derived neurotrophic factor (BDNF)-dependent neurons are killed by antisense bcl-2 RNA in the presence of BDNF. However, when these neurons were supported with ciliary neurotrophic factor (CNTF) their survival was not affected by antisense bcl-2 RNA. Likewise, the survival of CNTF-dependent ciliary neurons was not affected by antisense bcl-2 RNA. Our findings suggest that Bcl-2 is required for the BDNF survival response and that alternative, Bcl-2-independent survival mechanisms operate in sensory and parasympathetic neurons exposed to CNTF.
Allsopp
T E
TE
School of Biological and Medical Sciences, St Andrews University, Fife, UK.
Kiselev
S
S
Wyatt
S
S
Davies
A M
AM
D000818:Animals; D001483:Base Sequence; D019208:Brain-Derived Neurotrophic Factor; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D020934:Ciliary Neurotrophic Factor; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005726:Ganglia, Parasympathetic / Q000166:cytology / Q000187:drug effects; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D016372:RNA, Antisense / Q000494:pharmacology; D014278:Trigeminal Nuclei / Q000166:cytology / Q000187:drug effects
D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; D015335:Molecular Probes; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016372:RNA, Antisense; D016222:Fibroblast Growth Factor 2