Human skeletal muscle cytosols are refractory to cytochrome c-dependent activation of type-II caspases and lack APAF-1 (original) (raw)

Cell Death & Differentiation volume 6, pages 256–261 (1999)Cite this article

Abstract

Apoptotic regulatory mechanisms in skeletal muscle have not been revealed. This is despite indications that remnant apoptotic events are detected following exercise, muscle injury and the progression of dystrophinopathies. The recent elicitation of a cytochrome **c**-mediated induction of caspases has led to speculation regarding a cytochrome c mechanism in muscle. We demonstrate that cytosols from skeletal muscle biopsies from healthy human volunteers lack the ability to activate type-II caspases by a cytochrome **c**-mediated pathway despite the confirmed presence of both procaspase-3 and -9. This was not due to the presence of an endogenous inhibitor, as the muscle cytosols enhanced caspase activity when added to a control cytosol, subsequently activated by cytochrome c and dATP. In addition, we demonstrate that muscle cytosols lack the apoptosis protease activator protein-1 (APAF-1), both at the protein and mRNA levels. These data indicate that human skeletal muscle cells will be refractory to mitochondrial-mediated events leading to apoptosis and thus can escape a major pro-apoptotic regulatory mechanism. This may reflect an evolutionary adaptation of cell survival in the presence of the profusion of mitochondria required for energy generation in motility.

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Authors and Affiliations

  1. Institute of Environmental Medicine, Karolinska Institute, Box 210, Stockholm, S-17177, Sweden
    David H Burgess, Michael Svensson, Tiziana Dandrea, Karina Grönlund, Sten Orrenius & Ian A Cotgreave
  2. Department of Physiology and Pharmacology, Karolinska Institute, Box 5626, Stockholm, 11486, Sweden
    Michael Svensson
  3. Department of Surgery, St. Gôrans Hospital, Stockholm, Sweden
    Folke Hammarquist

Authors

  1. David H Burgess
  2. Michael Svensson
  3. Tiziana Dandrea
  4. Karina Grönlund
  5. Folke Hammarquist
  6. Sten Orrenius
  7. Ian A Cotgreave

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Correspondence toIan A Cotgreave.

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Edited by: G. Melino

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Burgess, D., Svensson, M., Dandrea, T. et al. Human skeletal muscle cytosols are refractory to cytochrome _c_-dependent activation of type-II caspases and lack APAF-1.Cell Death Differ 6, 256–261 (1999). https://doi.org/10.1038/sj.cdd.4400489

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