Biphasic modulation by nitric oxide of caspase activation due to malonate injection in rat striatum
| Autor: | Isabelle Margaill, Bruno Palmier, Michel Plotkine, Alexia Paucard, Fanny Taillieu, Nicole Croci |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Gene isoform Indazoles 7-Nitroindazole Pharmacology Nitric Oxide medicine.disease_cause Nitric oxide Rats Sprague-Dawley chemistry.chemical_compound medicine Animals Caspase chemistry.chemical_classification biology Toxin Caspase Inhibitors Corpus Striatum Malonates Rats Malonate Enzyme chemistry Biochemistry Caspases biology.protein Oxidative stress |
| Zdroj: | European Journal of Pharmacology. 483:259-265 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2003.10.038 |
| Popis: | The present study examined caspase activation and its modulation by nitric oxide (NO) in a model of oxidative stress induced by injection of malonate (3 micromol), a mitochondrial toxin, into rat striatum. Caspase-3-like enzymatic activity was maximal 6 h after malonate while NO production evaluated by its metabolites nitrites and nitrates was increased at 3 h. The neuronal NO-synthase inhibitor 7-nitroindazole reduced malonate induced-NO production by 50% at 25 mg/kg and enhanced by 32% caspase activation. This result suggests that a moderate production of NO potentiates caspase activation, an effect counterbalanced by NO itself at higher concentrations. Accordingly, complete inhibition of NO production by 7-nitroindazole at 50 mg/kg did not modify malonate-induced caspase activity. Thus NO production by the neuronal isoform of NO-synthase is not the major event leading to caspase activation due to malonate. However, NO seems to have pro- and anti-caspase effects that neutralize each other. |
| Databáze: | OpenAIRE |
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