| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
and NF-
B in
perinatal lung epithelium requires glutathione
biosynthesis
Oxygen Signalling Group, Tayside Institute of Child Health, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, United Kingdom
To test the genetic
capacity of the perinatal lung to respond to O2 shifts that
coincide with the first respiratory movements, rat fetal alveolar type
II (fATII) epithelial cells were cultured at fetal distal lung
PO2 (23 Torr) and then exposed to postnatal (23 
76 Torr; mild hyperoxic shift), moderate (23 152 Torr; moderate hyperoxic shift), or severe (23 722 Torr; severe hyperoxic shift) oxygenation. Nuclear abundance and
consensus binding characteristics of hypoxia-inducible factor
(HIF)-1
and nuclear factor (NF)-
B (Rel A/p65) plus glutathione
biosynthetic capacity were determined. Maximal HIF-1 activation at
23 Torr was sustained over the postnatal shift in (
)
PO2 and was elevated in vivo
throughout late gestation. NF-B was activated by the acute postnatal
PO2 in fATII cells, becoming maximal with moderate and severe oxygenation in vitro and within 6 h of
birth in vivo, declining thereafter. fATII cell and whole lung
glutathione and GSH-to-GSSG ratio increased fourfold with a postnatal
PO2 and were matched by threefold
activity increases in 
-glutamylcysteine synthetase and glutathione
synthase. GSH concentration depletion by
L-buthionine-(S,R)-sulfoximine abrogated both
HIF-1 and NF-B activation, with HIF-1 showing a heightened
sensitivity to GSH concentration. We conclude that O2-linked genetic regulation in perinatal lung epithelium
is responsive to developmental changes in glutathione biosynthetic capacity.
hypoxia-inducible factor-1; nuclear factor-B; lung
development; L-buthionine-(S,R)-sulfoximine; transcription factor; antioxidant; bronchopulmonary
dysplasia
This article has been cited by other articles:
|
|
 |
|
  C. Balestra, P. Germonpre, J. R. Poortmans, and A. Marroni Serum erythropoietin levels in healthy humans after a short period of normobaric and hyperbaric oxygen breathing: the "normobaric oxygen paradox" J Appl Physiol, February 1, 2006; 100(2): 512 - 518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fratelli, L. O. Goodwin, U. A. Orom, S. Lombardi, R. Tonelli, M. Mengozzi, and P. Ghezzi Gene expression profiling reveals a signaling role of glutathione in redox regulation PNAS, September 27, 2005; 102(39): 13998 - 14003. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. D. Mansfield, M. C. Simon, and B. Keith Hypoxic reduction in cellular glutathione levels requires mitochondrial reactive oxygen species J Appl Physiol, October 1, 2004; 97(4): 1358 - 1366. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Tissot van Patot, J. Bendrick-Peart, V. E. Beckey, N. Serkova, and L. Zwerdlinger Greater vascularity, lowered HIF-1/DNA binding, and elevated GSH as markers of adaptation to in vivo chronic hypoxia Am J Physiol Lung Cell Mol Physiol, September 1, 2004; 287(3): L525 - L532. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. E. Bickler Clinical perspectives: neuroprotection lessons from hypoxia-tolerant organisms J. Exp. Biol., August 15, 2004; 207(18): 3243 - 3249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nikinmaa, S. Pursiheimo, and A. J. Soitamo Redox state regulates HIF-1{alpha} and its DNA binding and phosphorylation in salmonid cells J. Cell Sci., July 1, 2004; 117(15): 3201 - 3206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. B. Suliman, M. Ali, and C. A. Piantadosi Superoxide dismutase-3 promotes full expression of the EPO response to hypoxia Blood, July 1, 2004; 104(1): 43 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. E. Bickler and P. H. Donohoe Adaptive responses of vertebrate neurons to hypoxia J. Exp. Biol., December 1, 2002; 205(23): 3579 - 3586. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Haddad, S. C. Land, W. O. Tarnow-Mordi, M. Zembala, D. Kowalczyk, and R. Lauterbach Immunopharmacological Potential of Selective Phosphodiesterase Inhibition. I. Differential Regulation of Lipopolysaccharide-Mediated Proinflammatory Cytokine (Interleukin-6 and Tumor Necrosis Factor-alpha ) Biosynthesis in Alveolar Epithelial Cells J. Pharmacol. Exp. Ther., February 1, 2002; 300(2): 559 - 566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Haddad, S. C. Land, W. O. Tarnow-Mordi, M. Zembala, D. Kowalczyk, and R. Lauterbach Immunopharmacological Potential of Selective Phosphodiesterase Inhibition. II. Evidence for the Involvement of an Inhibitory-kappa B/Nuclear Factor-kappa B-Sensitive Pathway in Alveolar Epithelial Cells J. Pharmacol. Exp. Ther., February 1, 2002; 300(2): 567 - 576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Haddad and S. C. Land Amiloride Blockades Lipopolysaccharide-Induced Proinflammatory Cytokine Biosynthesis in an Ikappa B-alpha /NF-kappa B-Dependent Mechanism . Evidence for the Amplification of an Antiinflammatory Pathway in the Alveolar Epithelium Am. J. Respir. Cell Mol. Biol., January 1, 2002; 26(1): 114 - 126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. E. Haddad, B. Safieh-Garabedian, N. E. Saadé, and S. C. Land Thiol Regulation of Pro-Inflammatory Cytokines Reveals a Novel Immunopharmacological Potential of Glutathione in the Alveolar Epithelium J. Pharmacol. Exp. Ther., March 1, 2001; 296(3): 996 - 1005. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
