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.
The signaling pathways implicated in regulating apoptosisin 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.
Haddad
J J
JJ
Oxygen Signaling Group, Center for Research into Human Development, Tayside Institute for Child Health, Faculty of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom. j.j.haddad@dundee.ac.uk
Choudhary
K K
KK
Land
S C
SC
D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D005260:Female; D005865:Gestational Age; D008168:Lung / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D010100:Oxygen / Q000502:physiology; D010920:Placenta / Q000502:physiology; D011247:Pregnancy; D011506:Proteins / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D012119:Respiration; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein
D000199:Actins; C494828:Bax protein, rat; C000715470:MAS1 protein, human; D011506:Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D010100:Oxygen