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

Uteroplacental insufficiency decreases p53 serine-15 phosphorylation in term IUGR rat lungs. Research Abstract Details 

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Uteroplacental insufficiency decreases p53 serine-15 phosphorylation in term IUGR rat lungs. Abstract Text:

E A O'Brien,V Barnes,L Zhao,R A McKnight,X Yu,C W Callaway,L Wang,J C Sun,M J Dahl,A Wint,Z Wang,T M McIntyre,K H Albertine,R H Lane,

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.

Uteroplacental insufficiency decreases p53 serine-15 phosphorylation in term IUGR rat lungs. Publishing Authors By Initials

EA O'Brien,V Barnes,L Zhao,RA McKnight,X Yu,CW Callaway,L Wang,JC Sun,MJ Dahl,A Wint,Z Wang,TM McIntyre,KH Albertine,RH Lane,

For similar proteins: dna-binding proteins: tumor suppressor protein p53 research abstracts see: proteins: dna-binding proteins: tumor suppressor protein p53 research

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Uteroplacental insufficiency decreases p53 serine-15 phosphorylation in term IUGR rat lungs. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: American journal of physiology. Regulatory, integr

VOLUME: 293

Page Numbers: R314-22

Journal Abbreviation: Am. J. Physiol. Regul. Integr.

ISSN: 0363-6119

DAY: 11

MONTH: 04

YEAR: 2007

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

Number of References:

LANGUAGE: eng

NlmUniqueID: 100901230

Uteroplacental insufficiency decreases p53 serine-15 phosphorylation in term IUGR rat lungs. Keywords Mesh Terms:

KEYWORDS: Tumor Suppressor Protein p53

MESH TERMS: metabolism

Chemical & Substance for Abstract: Uteroplacental insufficiency decreases p53 serine-15 phosphorylation in term IUGR rat lungs. Information

Substance Name: Protein Kinases

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Uteroplacental insufficiency decreases p53 serine-15 phosphorylation in term IUGR rat lungs.

AFFILIATION: Division of Neonatology, University of Utah, Salt Lake City, UT 84158, USA. elizabeth.obrien@hsc.utah.edu

Country: United States

AGENCY: United States NCRR

GRANT: M01 RR 018390

ACRONYM: RR

MEDLINETA: Am J Physiol Regul Integr Comp

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