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Sepsis stimulates release of myofilaments in skeletal muscle by a calcium‐dependent mechanism
Author(s) -
Williams Arthur B.,
DecourtenMyers Gabrielle M.,
Fischer Josef E.,
Luo Guangju,
Sun Xiaoyan,
Hasselgren PerOlof
Publication year - 1999
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.13.11.1435
Subject(s) - myofilament , myofibril , myosin , skeletal muscle , calpain , actin , calcium , microbiology and biotechnology , protein degradation , chemistry , medicine , biology , endocrinology , biochemistry , enzyme
Sepsis is associated with a pronounced catabolic response in skeletal muscle, mainly reflecting degradation of the myofibrillar proteins actin and myosin. Recent studies suggest that sepsis‐induced muscle proteolysis may reflect ubiquitin‐proteasome‐dependent protein breakdown. An apparently conflicting observation is that the ubiquitin‐proteasome pathway does not degrade intact myofibrils. Thus, it is possible that actin and myosin need to be released from the myofibrils before they can be ubiquitinated and degraded by the proteasome. We tested the hypothesis that sepsis results in disruption of Z‐bands, increased expression of calpains, and calcium‐dependent release of myofilaments in skeletal muscle. Sepsis induced in rats by cecal ligation and puncture resulted in increased gene expression of μ‐calpain, m‐calpain, and p94 and in Z‐band disintegration in the extensor digitorum longus muscle. The release of myofilaments from myofibrillar proteins was increased in septic muscle. This response to sepsis was blocked by treating the rats with dantrolene, a substance that inhibits the release of calcium from intracellular stores to the cytoplasm. The present results provide evidence that sepsis is associated with Z‐band disintegration and a calcium‐dependent release of myofilaments in skeletal muscle. Release of myofilaments may be an initial and perhaps rate‐limiting component of sepsis‐induced muscle breakdown.—Williams, A. B., deCourten‐Myers, G. M., Fischer, J. E., Luo, G., Sun, X., Hasselgren, P.‐O. Sepsis stimulates release of myofilaments in skeletal muscle by a calcium‐dependent mechanism. FASEB J. 13, 1435–1443 (1999)