AJP - Regulatory, Integrative and Comparative Physiology, Vol 272, Issue 3 849-R856, Copyright © 1997 by American Physiological Society

ARTICLES

Intracellular regulation of protein degradation during sepsis is different in fast- and slow-twitch muscle

G. Tiao, M. Lieberman, J. E. Fischer and P. O. Hasselgren
Department of Surgery, University of Cincinnati, Ohio 45267-0558, USA.

We tested the hypothesis that the difference in the response to sepsis of protein breakdown between fast- and slow-twitch skeletal muscle reflects differential activation of the energy-ubiquitin-dependent proteolytic pathway. In addition, we defined the time course and the tissue specificity of sepsis-induced changes in the expression of the ubiquitin pathway. Sepsis was induced in rats by cecal ligation and puncture; control rats were sham operated. Energy-dependent protein breakdown was measured in incubated extensor digitorum longus (EDL) and soleus muscles. Ubiquitin mRNA levels were determined by Northern blot analysis. Sepsis resulted in increased energy-dependent protein breakdown and upregulated expression of ubiquitin mRNA in the fast-twitch EDL but not in the slow-twitch soleus muscle. The sepsis-induced increase in ubiquitin mRNA levels in the EDL muscle was noticeable before the increase in energy-dependent protein breakdown. Sepsis increased ubiquitin mRNA levels in the diaphragm (a mixed fiber-type muscle) but not in heart, liver, kidney, or intestine, consistent with a tissue-specific regulation of the ubiquitin system during sepsis. The results suggest that the difference in protein breakdown during sepsis between fast- and slow-twitch muscles reflects differential activation of the energy-ubiquitin-dependent proteolytic pathway. The data also suggest that the expression of the ubiquitin pathway is upregulated in a time-dependent fashion during sepsis and that this response is not a generalized phenomenon but is tissue specific.

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