The ex Vivo Differential Expression of Apoptosis Signaling Cofactors in the Developing Perinatal Lung: Essential Role of Oxygenation During the Transition from Placental to Pulmonary-Based Respiration

John J. E. Haddad, Kunal K. Choudhary, Stephen C. Land

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The signaling pathways implicated in regulating apoptosis in the perinatal developing lung are not well characterized. We have previously shown that apoptosis signaling cofactors in the fetal alveolar epithelium are redox-sensitive and differentially expressed in response to oxyexcitation (Haddad and Land, Biochem. Biophys. Res. Commun. 271, 257-267, 2000). In this report we investigated the role of oxygenation during the transition period from placental to pulmonary-based respiration in regulating the differential expression of apoptosis cofactors ex vivo. The antiapoptotic proto-oncogene, Bcl-2, exhibited suppressed abundance commencing after birth, an effect which was partially restored at a later stage of development. Oxygenation-mediated down-regulation of Bcl-2 was accompanied by suppression of Bax, such that Bcl-2/Bax equilibrium ratio remained steadily constant postnatally. Analysis of whether a Bax-independent pathway is involved in cell death in the perinatal lung revealed a novel role for p53, whose abundance predominated that of Bcl-2 and Bax at different stages of gestational development. We conclude that apoptosis ex vivo is partly Bax-insensitive and mediated by suppression of Bcl-2 in a p53-dependent mechanism.

Original languageEnglish
Pages (from-to)311-316
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume281
Issue number2
DOIs
Publication statusPublished - 23 Feb 2001

Keywords

  • Agonism/antagonism equilibrium
  • Apoptosis
  • Birth
  • Development
  • Oxygenation
  • Placental/pulmonary respiration

Fingerprint Dive into the research topics of 'The <i>ex Vivo</i> Differential Expression of Apoptosis Signaling Cofactors in the Developing Perinatal Lung: Essential Role of Oxygenation During the Transition from Placental to Pulmonary-Based Respiration'. Together they form a unique fingerprint.

  • Cite this