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A Possible Mechanism of Adriamycin Cardiotoxicity

Inhibition of NADP-Linked Isocitrate Dehydrogenase

  • Chapter
Advances in Myocardiology

Abstract

In heart muscle, NADP-linked isocitrate dehydrogenase activity is particularly high when compared with that of the other representative NADPH-generating enzyme, glucose-6-phosphate dehydrogenase. Approximately 80% of cardiac NADP-linked isocitrate dehydrogenase activity originates in the mitochondria. Adriamycin inhibited the activity of both mitochondrial and cytoplasmic NADP-linked isocitrate dehydrogenase dose dependently but had no effect on glucose-6-phosphate dehydrogenase. The inhibition was kinetically distinguished as noncompetitive. Preincubation of crude cardiac enzyme preparations with adriamycin enhanced the inhibition time dependently for 45 min. However, there was no evidence to suggest that the metabolites of adriamycin produced in this system were active as inhibitors. Adria-mycin-binding protein was fractionated by affinity chromatography, but NADP-linked isocitrate dehydrogenase activity was not detected in this fraction.

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Authors and Affiliations

  1. Second Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602, Japan

    T. Minaga, M. Yasumi, K. Nakamura, I. Kimura, A. Kizu & H. Ijichi

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  1. T. Minaga
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  2. M. Yasumi
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  3. K. Nakamura
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  4. I. Kimura
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  5. A. Kizu
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  6. H. Ijichi
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Editor information

Editors and Affiliations

  1. Cardiology Research Center, Academy of Medical Sciences, Moscow, USSR

    E. Chazov M.D.

  2. Institute of Pathology, McGill University, Montreal, Quebec, Canada

    G. Rona M.D.

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© 1983 Springer Science+Business Media New York

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Minaga, T., Yasumi, M., Nakamura, K., Kimura, I., Kizu, A., Ijichi, H. (1983). A Possible Mechanism of Adriamycin Cardiotoxicity. In: Chazov, E., Saks, V., Rona, G. (eds) Advances in Myocardiology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-4441-5_22

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  • DOI: https://doi.org/10.1007/978-1-4757-4441-5_22

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-4443-9

  • Online ISBN: 978-1-4757-4441-5

  • eBook Packages: Springer Book Archive

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