Nonresponsiveness of cerebral p53-MDM2 functional circuit in newborn rat pups rendered IUGR via uteroplacental insufficiency

• DOI: 10.1152/ajpregu.00701.2004
• Publication Date: 2004-11-25T01:24:02Z
• Authors: Xingrao Ke; Robert A. McKnight; Zheng-ming Wang; Xing Yu; Laiyi Wang; Christopher W. Ca...; Kurt H. Albertine; Robert H. Lane
• Keywords: Placental insufficiency

Severe uteroplacental insufficiency causes cerebral apoptosis in the fetus. Moderate intrauterine growth retardation (IUGR) and increases risk of postnatal neurological morbidity. In rat, IUGR affect gene expression Bcl-2 predispose newborn rat toward when challenged with perinatal hypoxia. Expression Bcl-2, as well proapoptotic protein Bax, is regulated by p53. p53 also induces MDM2 transcription, which functions to limit further p53-induced apoptosis. The predisposition fetus suggests that p53-MDM2 “functional” circuit may be perturbed brain. We hypothesized does not increase response increased or levels phospho-p53 (Ser15), an activated form To prove this hypothesis, we induced through bilateral uterine ligation pregnant rat. Uteroplacental significantly mRNA, total protein, (Ser15) brain at term. Increased terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells were localized CA1 region hippocampus, subcortical periventricular white matter, amygdala contrast, decreased mRNA phospho-MDM2 (Ser166) pups. conclude present pup, speculate contributes long-term neurodevelopmental morbidities.