Peroxynitrite-induced oligodendrocyte toxicity is not dependent on poly(ADP-ribose) polymerase activation
| Autor: | László Virág, Csaba Szabó, Gwen S. Scott, D. Craig Hooper |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Programmed cell death
Necrosis Poly ADP ribose polymerase Biology Oligodendrocyte Cell biology Cellular and Molecular Neuroscience chemistry.chemical_compound medicine.anatomical_structure Neurology chemistry Biochemistry medicine Neuroglia Viability assay medicine.symptom Cytotoxicity Peroxynitrite |
| Zdroj: | Glia. 41:105-116 |
| ISSN: | 0894-1491 |
| DOI: | 10.1002/glia.10137 |
| Popis: | Oligodendrocyte loss is a characteristic feature of several CNS disor- ders, including multiple sclerosis (MS) and spinal cord injury. However, the mechanisms responsible for oligodendrocyte destruction remain undefined. As recent studies have implicated peroxynitrite in the pathogenesis of both spinal cord injury and MS, we have examined whether peroxynitrite may mediate at least some of the oligodendrocyte damage and demyelination observed in these conditions. Primary rat oligodendrocytes were exposed to authentic peroxynitrite in vitro and assessed for cytotoxicity. Mitochon- drial function, measured by the reduction of MTT to formazan, and mitochondrial membrane potential were used as indicators of cell viability. Cell death was quantitated by measuring either the release of lactate dehydrogenase from, or the uptake of pro- pidium iodide into, damaged and dying cells. Peroxynitrite dose-dependently reduced the viability of primary oligodendrocytes and induced cell death. Furthermore, peroxyni- trite significantly increased DNA strand breakage and the activity of poly(ADP-ribose) polymerase (PARP) in oligodendrocyte cultures. To identify whether PARP activation plays a role in peroxynitrite-induced oligodendrocyte toxicity, we examined the effects of the PARP inhibitors 3-aminobenzamide (3AB) and 5-iodo-6-amino-1,2-benzopyrone (INH2BP) on mitochondrial function and cell death in oligodendrocytes. The presence of 3AB and INH2BP did not protect oligodendrocytes from peroxynitrite-induced cytotox- icity. However, both compounds significantly reduced PARP activity in these cells. Primary oligodendrocytes generated from PARP-deficient mice were also highly suscep- tible to peroxynitrite-induced cell death. Therefore, our results show that peroxynitrite exerts cytotoxic effects on oligodendrocytes in vitro independently of PARP activation. GLIA 41:105-116, 2003. © 2003 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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