title: Heme oxygenase-1 induction protects murine cortical astrocytes from hemoglobin toxicity.
abstract: Exposure to micromolar concentrations of hemoglobin (Hb) results in the oxidative death of cultured cortical neurons, but glia are resistant. The role of heme oxygenase-1 (HO-1) induction on this glial resistance was investigated. Within two hours of exposure to 5 microM Hb, immunoblotting demonstrated an increase in HO-1 in confluent glial cultures. Consistent with prior observations, 23-30 h Hb exposure had little or no effect on glial viability, as assessed by lactate dehydrogenase release. Concomitant treatment with the HO inhibitors tin protoporphyrin IX or the D-amino acid peptide rvnlrialry resulted in release of 40-71% of glial lactate dehydrogenase; protein synthesis inhibition with cycloheximide produced a similar effect. These results are consistent with the hypothesis that HO-1 induction protects cortical astrocytes from Hb toxicity.
authors.affiliation: Division of Emergency Medicine, Thomas Jefferson University, 1020 Sansom Street, 239 Thompson, Philadelphia, USA. raymond.f.regan@mail.tju.edu
authors.forename: R F
authors.initials: RF
authors.lastname: Regan
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
authors.forename: N
authors.initials: N
authors.lastname: Kumar
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000201:enzymology* / Q000473:pathology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000201:enzymology* / Q000473:pathology; D004790:Enzyme Induction; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D051547:Heme Oxygenase-1; D006441:Hemoglobin A / Q000378:metabolism* / Q000633:toxicity; D008565:Membrane Proteins; D051379:Mice; D009457:Neuroglia / Q000201:enzymology / Q000473:pathology; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D016877:Oxidants / Q000378:metabolism* / Q000633:toxicity
chemical_list: D008565:Membrane Proteins; D016877:Oxidants; D006441:Hemoglobin A; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse