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 language | English |
|---|---|
| Pages (from-to) | 311-316 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 281 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 23 Feb 2001 |
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Keywords
- Agonism/antagonism equilibrium
- Apoptosis
- Birth
- Development
- Oxygenation
- Placental/pulmonary respiration
Cite this
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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. / Haddad, John J. E.; Choudhary, Kunal K.; Land, Stephen C.
In: Biochemical and Biophysical Research Communications, Vol. 281, No. 2, 23.02.2001, p. 311-316.Research output: Contribution to journal › Article
TY - JOUR
T1 - The ex Vivo Differential Expression of Apoptosis Signaling Cofactors in the Developing Perinatal Lung
T2 - Essential Role of Oxygenation During the Transition from Placental to Pulmonary-Based Respiration
AU - Haddad, John J. E.
AU - Choudhary, Kunal K.
AU - Land, Stephen C.
PY - 2001/2/23
Y1 - 2001/2/23
N2 - 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.
AB - 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.
KW - Agonism/antagonism equilibrium
KW - Apoptosis
KW - Birth
KW - Development
KW - Oxygenation
KW - Placental/pulmonary respiration
UR - http://www.scopus.com/inward/record.url?scp=0034808954&partnerID=8YFLogxK
U2 - 10.1006/bbrc.2001.4350
DO - 10.1006/bbrc.2001.4350
M3 - Article
VL - 281
SP - 311
EP - 316
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -