Heme oxygenase-1 induction protects murine cortical astrocytes from hemoglobin toxicity.
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.
Regan
R F
RF
Division of Emergency Medicine, Thomas Jefferson University, 1020 Sansom Street, 239 Thompson, Philadelphia, USA. raymond.f.regan@mail.tju.edu
Guo
Y
Y
Kumar
N
N
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
D008565:Membrane Proteins; D016877:Oxidants; D006441:Hemoglobin A; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse