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1779 Cell Death Genes are Induced Immediately after Hypoxia-Reoxygenation (HR) in the Newborn Mouse Lung
  1. EJ Wollen1,2,
  2. AGW Rognlien1,2,
  3. M Atneosen-Åsegg2,3,
  4. MS Wright1,
  5. M Bjørås4,
  6. OD Saugstad1,2
  1. 1Department of Pediatric Research, Oslo University Hospital HF
  2. 2Women and Childreńs Division, University of Oslo, Oslo
  3. 3Department of Clinical Molecular Biology and Laboratory Sciences, Akershus University Hospital, Lørenskog
  4. 4Department of Microbiology, Oslo University Hospital HF, Oslo, Norway

Abstract

Background and Aims HR-injury can induce generation of reactive oxygen species which activate anti-/pro-apoptotic signalling in the cell or cause direct cell damage. The lungs of newborn neonates are susceptible to HR-injury. To explore underlying mechanisms, a temporal profile of a priori selected genes was performed.

Methods 84 C57BL/6 mice postnatal day 7 were randomized to 120 min of hypoxia (FiO2 0.08, n=64) or 180 min in air (C21, n=20). The hypoxia group was further randomized to 30 min reoxygenation with FiO2 0.60 (H60) or air (H21). Lung tissue was harvested after observation in air for 0, 150, 300 min or 3 days and 44 mRNA transcripts were analyzed by real-time PCR.

Results Bcl2, Bcl2l1, Bnip3 and Gadd45g were significantly up- regulated (p<0.05), and Ccnd1, Chek1 and Casp3 down-regulated in H60vsC21 and H21vsC21 (0 min). Apex1 and Apaf1 were also down-regulated in the comparison H60vsC21. After 150 min Apex1, Bcl2, Casp3, Ccnd1, Chek1 and Mutyh were down-regulated for H60vsC21 and H21vsC21. Bcl2 continued to be down-regulated in both comparisons (300 min). Gadd45g was only up-regulated in H60vsC21 after 150 and 300 min. No significant gene expression changes were observed after 3 days.

Conclusion HR-injury in the newborn lung induces an immediate alteration in the expression of both anti- (Bcl2, Bcl2l1) and pro-apoptotic genes (Bnip3, Apaf1, Apex1, Gadd45g), while cell-cycle genes (Ccnd1, Chek1) are suppressed. A suppression of Bcl2 from 150 min and a continuous up-regulation of Gadd45g after hyperoxic reoxygenation may indicate early phase of DNA damage-induced apoptosis.

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