Heme oxygenase-2 gene deletion increases astrocyte vulnerability to hemin |
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Authors: | Chen Jing Regan Raymond F |
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Institution: | Department of Emergency Medicine, Thomas Jefferson University Hospital, 1020 Sansom Street, 239 Thompson Building, Philadelphia, PA 19107, USA. |
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Abstract: | 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. |
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Keywords: | Free radical Hemoglobin Brain hemorrhage Iron Mouse Oxidative stress Stroke |
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