Expression of bcl-2, bax, and caspase-3 in the brain of the developing rat.
Naturally occurring neuronal death (NOND) is generally considered to be apoptotic. Apoptosis is an active form of cell death in which the regulation of specific proteins produces anti- or pro-apoptotic signals. Two of the protein families involved in this regulation are the bcl proteins and caspases. A quantitative immunoblotting technique was used to examine the temporal expression of bcl-2, bax, and two isoforms of caspase 3 (an active 20 kDa isoform and the inactive 32 kDa precursor) throughout the developing neuraxis. Long-Evans rat fetuses were collected on gestational day (G) 16 and G19, and pups were harvested on postnatal day (P) 0, P3, P6, P12, P21, and P30. Brains were divided into five segments: cortex, thalamus, midbrain, medulla/pons, and cerebellum. In general, the expression of bax increased and the ratio of bcl-2 expression to bax expression decreased concurrent with published data on the onset of NOND in a given area. The timing of these events was paralleled by an increase in the expression of active caspase 3. Unlike the bcl proteins, caspase 3 expression returned toward fetal levels as the brain matured. The timing of the changes in bcl protein and caspase expression show that both protein families are involved in promoting neuronal death. Reductions in caspase expression (and not bcl-2 and bax expression) are key to ending the period of NOND.
Mooney
S M
SM
Department of Psychiatry, University of Iowa College of Medicine, Iowa City, IA 52242-1000, USA.
Miller
M W
MW
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000254:growth & development*; D001923:Brain Chemistry / Q000235:genetics / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D019254:Genes, bcl-2 / Q000235:genetics / Q000502:physiology*; D015151:Immunoblotting; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D009474:Neurons / Q000502:physiology; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D020318:Rats, Long-Evans; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D007527:Isoenzymes; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases