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Tnf-α and IL-1α inhibit both pyruvate dehydrogenase activity and mitochondrial function in cardiomyocytes: Evidence for primary impairment of mitochondrial function

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Abstract

Cytokines such as tumor necrosis factor α (TNFα) and Interleukin-1α (IL1α) are known to influence energy metabolism and mitochondrial function in tumor and vascular smooth muscle cells. The aim of the present study was to investigate whether in cardiomyocytes mitochondrial function and PDH activity may also be impaired by TNFα and IL1α. Pyruvate dehydrogenase (PDH) activity and mitochondrial oxygen consumption of cultured cardiomyocytes were determined after subchronic exposure (24 h) to TNFα (1, 10, 100, 1000 I.U./ml) and IL1α (0.1, 1, 10, 100 I.U./ ml).

TNFα- and IL1α- exposure of the cardiomyocytes resulted in a concentration dependent decrease of PDH activity up to 38%. In parallel, selective oxygen consumption of the respiratory chain complexes I (NADH:ubiquinone oxidoreductase) and II (succinate:ubiquinone oxidoreductase) decreased by up to 45%. Addition of the PDH activator dichloracetate (0.01 M) resulted in complete restoration of PDH activity but not of mitochondrial function. The results suggest a primary inhibition of the mitochondrial respiratory chain by TNFα and IL1α and a subsequent down regulation of PDH activity.

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Authors and Affiliations

  1. Department of Internal Medicine I, Klinikum Großhadern, University of Munich, Germany

    Robert Zell & Peter Boekstegers

  2. Gustav Embden Center of Biological Chemistry, University of Frankfurt, Germany

    Peter Geck

  3. Department of Internal Medicine, Klinikum Kröllwitz, University of Halle-Wittenberg, Germany

    Karl Werdan

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  1. Robert Zell
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  2. Peter Geck
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  3. Karl Werdan
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  4. Peter Boekstegers
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Zell, R., Geck, P., Werdan, K. et al. Tnf-α and IL-1α inhibit both pyruvate dehydrogenase activity and mitochondrial function in cardiomyocytes: Evidence for primary impairment of mitochondrial function. Mol Cell Biochem 177, 61–67 (1997). https://doi.org/10.1023/A:1006896832582

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