Uteroplacental Insufficiency Lowers the Cerebral Threshold towards Hypoxia Induced Apoptosis in Fetal Rats

Lane, Robert H.; Ramierez, Rolondo J; Tsirka, Anna E.; Kloesz, Jennifer L; Gruetzmacher, Elisa M

doi:10.1203/00006450-199904020-00334

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The method of Chomczynski and Sacchi was used to isolate RNA, as previously described, including treatment with DNase (40,42,58,71,75). Gel electrophoresis confirmed the integrity of the samples.…”

Section: Methodsmentioning

confidence: 99%

Uteroplacental insufficiency decreases p53 serine-15 phosphorylation in term IUGR rat lungs

O’Brien

Barnes

Zhao

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Intrauterine growth restriction (IUGR) increases the incidence of chronic lung disease (CLD). The molecular mechanisms responsible for IUGR-induced acute lung injury that predispose the IUGR infant to CLD are unknown. p53, a transcription factor, plays a pivotal role in determining cellular response to stress by affecting apoptosis, cell cycle regulation, and angiogenesis, processes required for thinning of lung mesenchyme. Because thickened lung mesenchyme is characteristic of CLD, we hypothesized that IUGR-induced changes in lung growth are associated with alterations in p53 expression and/or modification. We induced IUGR through bilateral uterine artery ligation of pregnant rats. Uteroplacental insufficiency significantly decreased serine-15-phosphorylated (serine-15P) p53, an active form of p53, in IUGR rat lung. Moreover, we found that decreased phosphorylation of lung p53 serine-15 localized to thickened distal air space mesenchyme. We also found that IUGR significantly decreased mRNA for targets downstream of p53, specifically, proapoptotic Bax and Apaf, as well as Gadd45, involved in growth arrest, and Tsp-1, involved in angiogenesis. Furthermore, we found that IUGR significantly increased mRNA for Bcl-2, an antiapoptotic gene downregulated by p53. We conclude that in IUGR rats, uteroplacental insufficiency induces decreased lung mesenchymal p53 serine-15P in association with distal lung mesenchymal thickening. We speculate that decreased p53 serine-15P in IUGR rat lungs alters lung phenotype, making the IUGR lung more susceptible to subsequent injury.

show abstract