The proto-oncogene bcl-2 can selectively rescue neurotrophic factor-dependent neurons from apoptosis.
Apoptosis plays an important role in regulating cell numbers in a wide variety of tissues during development. The product of the bcl-2 gene inhibits apoptosis in certain cells of the myeloid and lymphoid lineages and is expressed in many cells that have an extended life span. To assess the role of bcl-2 in neuronal apoptosis, we microinjected a bcl-2 expression vector into neurotrophic factor-deprived embryonic neurons. Sensory neurons that depend for survival on one or more members of the nerve growth factor family of neurotrophic factors (nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3) were rescued by bcl-2, whereas ciliary neurotrophic factor (CNTF)-dependent ciliary neurons were not. Sensory neurons, however, became refractory to bcl-2 after exposure to CNTF. These findings indicate that at least two death pathways operate in neurons that are distinguished by their susceptibility to bcl-2. Neurons may die by either pathway, depending on the factors to which they have been exposed.
Allsopp
T E
TE
School of Biological and Medical Sciences, St. Andrews, Fife, Scotland.
Wyatt
S
S
Paterson
H F
HF
Davies
A M
AM
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D019208:Brain-Derived Neurotrophic Factor; D002451:Cell Compartmentation; D002642:Chick Embryo; D020934:Ciliary Neurotrophic Factor; D003001:Cloning, Molecular; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009420:Nervous System / Q000196:embryology*; D009474:Neurons / Q000166:cytology*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; C000715470:MAS1 protein, human; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009838:Oligodeoxyribonucleotides; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011994:Recombinant Proteins