Chronic Alcohol Consumption Increases the Expression of Uncoupling Protein-2 and -4 in the Brain

Authors

  • Jan A. Graw,

    1. Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Berlin, Germany
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  • Clarissa von Haefen,

    1. Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Berlin, Germany
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  • Deniz Poyraz,

    1. Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Berlin, Germany
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  • Nadine Möbius,

    1. Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Berlin, Germany
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  • Marco Sifringer,

    1. Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Berlin, Germany
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  • Claudia D. Spies

    Corresponding author
    • Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Berlin, Germany
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  • Jan A. Graw and Clarissa von Haefen contributed equally to this work.

Reprint requests: Claudia D. Spies, MD, PhD, Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany; Tel.: +4930450551001; Fax: +4930450551900; E-mail: claudia.spies@charite.de

Abstract

Background

Chronic alcohol consumption leads to oxidative stress in a variety of cells, especially in brain cells because they have a reduced oxidative metabolism of alcohol. Uncoupling proteins (UCPs) are anion channels of the inner mitochondrial membrane, which can decouple internal respiration. “Mild uncoupling” of the mitochondrial respiratory chain leads to a reduced production of free radicals (reactive oxygen species) and a reduction in oxidative cell stress. The extent to which chronic alcohol consumption regulates UCP-2 and -4 in the brain is still unknown.

Methods

We examined the effects of a 12-week 5% alcohol diet in the brain of male Wistar rats (= 34). Cerebral gene and protein expression of UCP-2, -4, as well as Bcl-2, and the release of cytochrome c out of the mitochondria were detected by real-time polymerase chain reaction and Western blot analysis. The percentage of degenerated cells was determined by Fluoro–Jade B staining of brain slices.

Results

Brains of rats with a chronic alcohol diet showed an increased gene and protein expression of UCP-2 and -4. The expression of the antiapoptotic protein Bcl-2 in the brain of the alcohol-treated animals was decreased significantly, whereas cytochrome c release from mitochondria was increased. In addition increased neurodegeneration could be demonstrated in the alcohol-treated animals.

Conclusions

Chronic alcohol consumption leads to a cerebral induction of UCP-2 and -4 with a simultaneous decrease in the antiapoptotic protein Bcl-2, cytochrome c release from mitochondria and increased neurodegeneration. This study reveals a compensatory effect of UCP-2 and -4 in the brain during chronic alcohol consumption.

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