Heme oxygenase-2 gene deletion increases astrocyte vulnerability to hemin.
In a prior study, we observed that heme oxygenase-2 gene deletion protected murine cortical neurons from heme-mediated injury. In the course of these studies, constitutive HO-2 expression was observed in astrocyte cultures. The present study tested the hypothesis that astrocytes lacking the HO-2 gene would be less vulnerable to heme. Contrary to this hypothesis, gene deletion resulted in a 50-75% increase in cell death after 6h exposure to 30 or 60microM hemin, as measured by LDH release. A similar effect was observed when cell viability was assessed with the MTT assay. HO-2 gene deletion did not alter cellular expression of HO-1. The increased sensitivity of knockout astrocytes to hemin was reversed by increasing HO-1 expression by adenoviral gene transfer. These results suggest that heme oxygenase protects astrocytes from heme-mediated oxidative injury and highlight the disparate effect of HO in neurons and astrocytes.
Chen
Jing
J
Department of Emergency Medicine, Thomas Jefferson University Hospital, 1020 Sansom Street, 239 Thompson Building, Philadelphia, PA 19107, USA.
Regan
Raymond F
RF
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D005296:Ferrous Compounds / Q000378:metabolism; D017353:Gene Deletion; D018014:Gene Transfer Techniques; D006419:Heme Oxygenase (Decyclizing) / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D051547:Heme Oxygenase-1; D006427:Hemin / Q000633:toxicity*; D006801:Humans; D015151:Immunoblotting; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008858:Microscopy, Phase-Contrast
D005296:Ferrous Compounds; D008565:Membrane Proteins; C020748:ferrous sulfate; D006427:Hemin; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C105245:heme oxygenase-2