title: Molecular markers of oxidative stress vulnerability.
abstract: In astrocyte primary cultures of trisomy 16 mice, an animal model for Down's syndrome, protein oxidation was 50% higher than in diploid littermates. Exposure to 10 microM H2O2 or 50 microM kainic acid incremented protein oxidation in trisomic but not in diploid cultures. Studies on stress response genes showed that metallothionein (MT) level was 2-3 times higher in trisomy 16 than in diploid cultures. Kainic acid or H2O2 exposure increased the MT protein level in diploid cultures but failed to increase it in trisomy 16 mouse beyond its elevated basal level. The reduced responsiveness of MT to simulated oxidative stress may result in insufficient removal of ROS, which could partially explain the further increase of protein oxidation in trisomy 16 cultures. In contrast, Pb exposure increased MT in trisomy 16 and diploid primary cultures to a similar extent. The similar metal responsiveness of MT in both phenotypes indicated that MT in trisomic glial cultures was not yet maximally stimulated. The flawed redox sensitivity in trisomy 16 mouse suggests possible alterations in the binding activity of ROS-sensitive transcription factors on the MT promoter.
authors.affiliation: Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892, USA. hanbaui@fido.uhlbi.nih.gov
authors.forename: I
authors.initials: I
authors.lastname: Hanbauer
authors.forename: M
authors.initials: M
authors.lastname: Scortegagna
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005819:Genetic Markers; D051379:Mice; D018384:Oxidative Stress; D014314:Trisomy
chemical_list: D005819:Genetic Markers