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Mitochondrial ATP-sensitive potassium channels enhance angiotensin-induced oxidative damage and dopaminergic neuron degeneration. Relevance for aging-associated susceptibility to Parkinson’s disease

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Abstract

Recent studies have shown that renin–angiotensin system overactivation is involved in the aging process in several tissues as well as in longevity and aging-related degenerative diseases by increasing oxidative damage and inflammation. We have recently shown that angiotensin II enhances dopaminergic degeneration by increasing levels of reactive oxygen species and neuroinflammation, and that there is an aging-related increase in angiotensin II activity in the substantia nigra in rats, which may constitute a major factor in the increased risk of Parkinson’s disease with aging. The mechanisms involved in the above mentioned effects and particularly a potential angiotensin–mitochondria interaction have not been clarified. The present study revealed that activation of mitochondrial ATP-sensitive potassium channels [mitoK(ATP)] may play a major role in the angiotensin II-induced effects on aging and neurodegeneration. Inhibition of mitoK(ATP) channels with 5-hydroxydecanoic acid inhibited the increase in dopaminergic cell death induced by angiotensin II, as well as the increase in superoxide/superoxide-derived reactive oxygen species levels and the angiotensin II-induced decrease in the mitochondrial inner membrane potential in cultured dopaminergic neurons. The present study provides data for considering brain renin–angiotensin system and mitoK(ATP) channels as potential targets for protective therapy in aging-associated diseases such as Parkinson’s disease.

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Acknowledgments

The authors thank Pilar Aldrey and Iria Novoa for their excellent technical assistance. Funding: Spanish Ministry of Science and Innovation, Institute of Health Carlos III (RD06/0010/0013 and CIBERNED), FEDER, and Galician Government (XUGA).

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Authors and Affiliations

  1. Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, Faculty of Medicine, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain

    Jannette Rodriguez-Pallares, Juan Andres Parga, Belen Joglar, Maria Jose Guerra & Jose Luis Labandeira-Garcia

  2. Networking Research Center on Neurodegenerative Diseases (CIBERNED), Santiago de Compostela, Spain

    Jannette Rodriguez-Pallares, Juan Andres Parga, Belen Joglar, Maria Jose Guerra & Jose Luis Labandeira-Garcia

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  1. Jannette Rodriguez-Pallares
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  2. Juan Andres Parga
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  5. Jose Luis Labandeira-Garcia
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Correspondence to Jose Luis Labandeira-Garcia.

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Rodriguez-Pallares, J., Parga, J.A., Joglar, B. et al. Mitochondrial ATP-sensitive potassium channels enhance angiotensin-induced oxidative damage and dopaminergic neuron degeneration. Relevance for aging-associated susceptibility to Parkinson’s disease. AGE 34, 863–880 (2012). https://doi.org/10.1007/s11357-011-9284-7

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