The Mitochondrial ATP-Sensitive Potassium Channel Blocker 5-Hydroxydecanoate Inhibits Toxicity of 6-Hydroxydopamine on Dopaminergic Neurons
| Autor: | Juan A. Parga, Jose L. Labandeira-Garcia, Maria J. Guerra, Jannette Rodriguez-Pallares, Belen Joglar |
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| Rok vydání: | 2009 |
| Předmět: |
Potassium Channels
Time Factors Tyrosine 3-Monooxygenase ATP-sensitive potassium channel Dopamine Cell Count Mitochondrion Biology Tritium Toxicology Neuroprotection chemistry.chemical_compound Adrenergic Agents Mesencephalon Ethidium Glyburide Potassium Channel Blockers Animals Drug Interactions Channel blocker Oxidopamine Inner mitochondrial membrane Antihypertensive Agents Cells Cultured Membrane Potential Mitochondrial Neurons Analysis of Variance Dose-Response Relationship Drug Rhodamines General Neuroscience Diazoxide Dopaminergic Carbocyanines Embryo Mammalian Rats Cell biology nervous system chemistry Benzimidazoles Hydroxy Acids Reactive Oxygen Species Neuron death Decanoic Acids Neuroscience |
| Zdroj: | Neurotoxicity Research. 15:82-95 |
| ISSN: | 1476-3524 1029-8428 |
| Popis: | The neurotoxin 6-hydroxydopamine is commonly used in models of Parkinson's disease, and a potential factor in the pathogenesis of the disease. However, the mechanisms responsible for 6-hydroxydopamine-induced dopaminergic degeneration have not been totally clarified. Reactive oxygen species (ROS) derived from 6-OHDA uptake and intraneuronal autooxidation, extracellular 6-OHDA autooxidation, and microglial activation have been involved. The mitochondrial implication is controversial. Mitochondrial ATP-sensitive K (mitoK(ATP)) channels may provide a convergent target that could integrate these different mechanisms. We observed that in primary mesencephalic cultures and neuron-enriched cultures, treatment with the mitoK(ATP) channel blocker 5-hydroxydecanoate, inhibits the dopaminergic degeneration induced by low doses of 6-OHDA. Furthermore, 5-hydroxydecanoate blocks the 6-OHDA-induced decrease in mitochondrial inner membrane potential and inhibits 6-OHDA-induced generation of superoxide-derived ROS in dopaminergic neurons. The results suggest that low doses of 6-OHDA may generate low levels of ROS through several mechanisms, which may be insufficient to induce neuron death. However, they could act as a trigger to activate mitoK(ATP) channels, thereby enhancing ROS production and the subsequent dopaminergic degeneration. Furthermore, the present study provides additional data for considering mitoK(ATP) channels as a potential target for neuroprotection. |
| Databáze: | OpenAIRE |
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