Expression of p53 and ALZ-50 immunoreactivity in rat cortex: effect of prenatal exposure to ethanol.
Neuronal death is an active process that results in the upregulation of antigens recognized by ALZ-50 and p53. Since prenatal exposure to ethanol can induce the postnatal death of cortical neurons, we examined the effects of ethanol on the in vivo expression of both the ALZ-50-positive antigen and p53. Pregnant rats were fed one of three diets, a liquid diet containing ethanol (Et), an isocaloric and isonutritive diet (Ct), or chow and water (Ch). Segments of frontoparietal cortex from fetuses and pups were examined for ethanol-induced changes (a) in the expression of ALZ-50 and p53 immunoreactivity using a quantitative immunoblotting assay and (b) in the distribution of ALZ-50- and p53-positive cells using immunohistochemistry. In control rats, ALZ-50 identified a 56-kDa peptide that was transiently expressed postnatally and peak expression occurred on postnatal day (P) 6 to P12. In Et-treated rats, peak expression was attained earlier (on P3) and was about three times of that achieved in the controls. The anti-p53 antibody identified three proteins (28, 56, and 58 kDa). Peak expression in control rats occurred during the second postnatal week and only the 58-kDa protein was expressed in appreciable amounts in adult cortex. Each p53-positive protein was affected by ethanol exposure. The 28- and 56-kDa p53-positive proteins were affected by ethanol much in the same way as was the ALZ-50-positive antigen. That is, the timing and amount of peak expression were earlier and lower, respectively, in the Et-treated rats. The postnatal expression of the 58-kDa protein was halved following prenatal exposure to ethanol. Both ALZ-50 and anti-p53 immunoprecipitated proteins are p53- and ALZ-50-positive, respectively. Thus, ethanol alters the expression of the ALZ-50- and p53-positive proteins and presumably the timing of neuronal death in the developing cortex. The parallel effects of prenatal ethanol exposure on the 56-kDa ALZ-50-positive antigen and the 28- and 56-kDa p53-positive proteins and the coprecipitation of the proteins are consistent with the notion that ALZ-50 recognizes a form of p53.
Kuhn
P E
PE
Program in Cell and Developmental Biology, Rutgers University, Piscataway, New Jersey, 08854-1059, USA.
Miller
M W
MW
D000818:Animals; D000941:Antigens / Q000032:analysis / Q000096:biosynthesis*; D017209:Apoptosis / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011233:Precipitin Tests; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D020318:Rats, Long-Evans; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis*
C056167:Alzheimer's disease antigen; D000941:Antigens; D002492:Central Nervous System Depressants; D009419:Nerve Tissue Proteins; D016159:Tumor Suppressor Protein p53; D000431:Ethanol