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 apoptosis in the perinatal developing lung are not well characterized. We have previously shown that a poptosis signaling cofactors in the fetal alveolar epithelium are redox-sen sitive and differentially expressed in response to oxyexcitation (Haddad an d Land, Biochem, Biophys, Res. Commun. 271, 257-267, 2000), In this report we investigated the role of oxygenation during the transition period from p lacental to pulmonary-based respiration in regulating the differential expr ession of apoptosis cofactors ex vivo. The antiapoptotic proto-oncogene, Bc l-2, exhibited suppressed abundance commencing after birth, an effect which was partially restored at a later stage of development, Oxygenation-modiat ed down-regulation of Bcl-2 was accompanied by suppression of Bax, such tha t Bcl-2/Bax equilibrium ratio remained steadily constant postnatally, Analy sis of whether a Bax-independent pathway is involved in cell death in the p erinatal lung revealed a novel role for p53, whose abundance predominated t hat of Bcl-2 and Bax at different stages of gestational development. We con clude that apoptosis ex vivo is partly Bar-insensitive and mediated by supp ression of Bcl-2 in a p53-dependent mechanism. (C) 2001 Academic Press.