COMT-dependent protection of dopaminergic neurons by methionine, dimethionine and S-adenosylmethionine (SAM) against l-dopa toxicity in vitro
| Autor: | A. Prikhojan, Peter Werner, Melvin D. Yahr, Susan B. Bressman, Teodoro Bottiglieri, Nicole Rempel, Alessandro Di Rocco |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
S-Adenosylmethionine
medicine.medical_specialty Levodopa Methyltransferase Cell Survival Dopamine Catechols Biology Catechol O-Methyltransferase COMT inhibitor chemistry.chemical_compound Methionine Internal medicine medicine Animals Enzyme Inhibitors Molecular Biology Cells Cultured Neurons Catechol-O-methyl transferase General Neuroscience Dopaminergic Neurotoxicity Catechol O-Methyltransferase Inhibitors medicine.disease Rats Neuroprotective Agents Endocrinology nervous system chemistry Neurology (clinical) Developmental Biology medicine.drug |
| Zdroj: | Brain Research. 893:278-281 |
| ISSN: | 0006-8993 |
| Popis: | l -dopa may be toxic to dopamine neurons, possibly due to catechol-autoxidation. Catechols are O -methylated by catechol- O -methyltransferase (COMT) in a SAM consuming reaction, preventing the initiation of catechol autoxidation. We hypothesized that SAM or SAM-precursors ameliorate l -dopa neurotoxicity, in a COMT-dependent fashion. We tested this hypothesis in primary mesencephalic cultures by adding 200 μM l -dopa with 2 mM methionine or 1 mM dimethionine or 0.5 mM SAM with or without 0.2 μM of the COMT-inhibitor 2′, 5′-dinitrocatechol (OR 486). l -dopa was found to be neurotoxic as the surviving neurons had fewer and shorter processes. Methionine, dimethionine and SAM all protected DA neurons against damaged induced by l -dopa. The COMT inhibitor dinitrocatechol (DNC) completely abolished the protective effect against l -dopa toxicity. We conclude that supplementation with methionine, dimethionine or SAM ameliorates l -dopa neurotoxicity to dopamine neurons, while inhibition of COMT may aggravate or unmask l -dopa neurotoxicity. |
| Databáze: | OpenAIRE |
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