|Anne Gro W. Rognlien|
|Position:||PhD student, MD|
|Phone:||+47 23 07 24 93|
PhD project: Changes in gene-expression with time after hypoxia and reoxygenation
Anne Gro Wesenberg Rognlien, PFI
Embjørg Wollen, PFI
Monica Atneosen-Aasegg, PFI
Magnar Bjørås, Dept. of Microbiology (Supervisor)
Ola Didrik Saugstad, PFI (Main supervisor)
Asphyxia of the newborn is a major cause of death and disability worldwide. One of the types of injury after asphyxia is hypoxia-reoxygenation (HR) injury. PFI has developed a model where postnatal day 7 mice are subjected to hypoxia and reoxygenation with different FiO2, and we study changes in gene expression (mRNA) and protein concentrations in this model. Ogg1-/-, Mutyh-/- double knockout mice lack two DNA-glycosylases important in initializing the Base excision repair (BER) pathway. The BER pathway repairs oxidative DNA-injury, and Ogg1 and Mutyh repair oxidized Guanine (8-oxoG) lesions to prevent C:G to A:T mutations.
To study changes with time in the gene expression of 44 a priori selcted genes and the protein concentration of the most interesting genes after hypoxia and reoxygenation in our established mouse model, and to compare the changes in transcription between wild type mice and double knockout Ogg1 -/-, Mutyh -/- mice.
C57BL/6 mice and Ogg1 -/-, Mutyh -/- mice (postnatal day 7) were randomized to two hours of hypoxia (FiO2 0.08) or air (controls). The hypoxia group was further randomized to 30 min reoxygenation with FiO2 0.60 or air. After observation from 0 h to 3 days, organs were harvested. Homogenate of hippocampus and striatum and homogenate of lung has been analyzed for mRNA expression of 44 genes by real-time RT-PCR in both wild type and knockout mice, and for protein in wild type mice only.
Results and conclusions
Hyperoxic reoxygenation after hypoxia gives a stronger response in inflammatory genes (Cxcl10, Hmox1, Il1b, Nfkb1and Tgfb1) and less suppression of the DNA glycosylase Neil3 in wild type mice. Also, we identified three patterns of gene expression changes after hypoxia regardless of reoxygenation mode. The results from lung tissue and knockout mice are not yet published.
The Norwegian Research Council; The Laerdal Foundation; The Norwegian SIDS and Stillbirth Society; Renée og Bredo Grimsgaard's Stiftelse; Kvinne- og Barneklinikkens FU-fond; and Skibsreder Tom Wilhelmsens Stiftelse.
Rognlien AGW, Wollen E, Atnesen-Åsegg M, Saugstad OD: Increased expression of inflammatory genes in the neonatal mouse brain after hyperoxic reoxygenation (Submitted manuscript).
Gene expression changes in the brain of Ogg1/Mutyh knockout mice following a hypoxia-reoxygenation insult. Poster at the European Society of Pediatric Research meeting, Porto 2013.
DNA glycosylases protect the newborn mouse lung from apoptosis, cell cycle arrest and inflammation. 28th International Workshop on surfactant replacement, June 1st 2013, Helsinki, Finland. (Oral presentation).
Temporal Patterns of Gene Expression Profiles in the Neonatal Mouse Lung after Hypoxia-Reoxygenation
Neonatology, 111 (1), 45-54
Increased expression of inflammatory genes in the neonatal mouse brain after hyperoxic reoxygenation
Pediatr Res, 77 (2), 326-33
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