Bax promotes neuronal cell death and is downregulated during the development of the nervous system.
The Bcl-2 and Bcl-x proteins suppress programmed cell death, whereas Bax promotes apoptosis. We investigated the pattern of expression of Bcl-2, Bax and Bcl-x during neuronal differentiation and development. All three proteins were widely expressed in neonatal rats but, in the adult, Bax levels were 20- to 140-fold lower in the cerebral cortex, cerebellum and heart muscle, whereas Bcl-x was not downregulated in any of the tissues examined. In the cerebral cortex and cerebellum, the decrease in Bax levels occurred after the period of developmental cell death. Further, microinjection of a Bax expression vector into cultured sympathetic neurons, which depend on nerve growth factor for survival, induced apoptosis in the presence of survival factor and increased the rate of cell death after nerve growth factor withdrawal. This effect could be blocked by co-injection of an expression vector for Bcl-xL or for the baculovirus p35 protein, an inhibitor of caspases (ICE-like proteases). These results suggest that, during development, the sensitivity of neurons to signals that induce apoptosis may be regulated by modulating Bax levels and that Bax-induced death requires caspase activity.
Vekrellis
K
K
Eisai London Research Laboratories, University College London, UK.
McCarthy
M J
MJ
Watson
A
A
Whitfield
J
J
Rubin
L L
LL
Ham
J
J
D000375:Aging / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001921:Brain / Q000254:growth & development* / Q000378:metabolism; D002454:Cell Differentiation; D002470:Cell Survival; D002531:Cerebellum / Q000254:growth & development; D002540:Cerebral Cortex / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009928:Organ Specificity; D016716:PC12 Cells; D010446:Peptide Fragments / Q000737:chemistry; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494826:BAX protein, human; C494811:BCL2L1 protein, human; C494828:Bax protein, rat; C494813:Bcl2l1 protein, rat; D009414:Nerve Growth Factors; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein