Neurotoxicity Research

, Volume 15, Issue 1, pp 82–95 | Cite as

The Mitochondrial ATP-Sensitive Potassium Channel Blocker 5-Hydroxydecanoate Inhibits Toxicity of 6-Hydroxydopamine on Dopaminergic Neurons

  • J. Rodriguez-Pallares
  • J. A. Parga
  • B. Joglar
  • M. J. Guerra
  • J. L. Labandeira-Garcia
Article

Abstract

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.

Keywords

6-OHDA Mitok(ATP) channels Dopamine Parkinson’s disease Oxidative stress Mitochondria Neurodegeneration 

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • J. Rodriguez-Pallares
    • 1
    • 2
  • J. A. Parga
    • 1
    • 2
  • B. Joglar
    • 1
    • 2
  • M. J. Guerra
    • 1
    • 2
  • J. L. Labandeira-Garcia
    • 1
    • 2
  1. 1.Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, Faculty of MedicineUniversity of Santiago de CompostelaSantiagoSpain
  2. 2.Networking Research Center on Neurodegenerative Diseases (CIBERNED)SevillaSpain

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