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Sepsis-induced muscle proteolysis is prevented by a proteasome inhibitor in vivo.

Abstract：

:Sepsis-induced muscle proteolysis mainly reflects ubiquitin-proteasome-dependent protein degradation. The effect of in vivo administration of a proteasome inhibitor on muscle protein breakdown during sepsis is not known. We treated rats with the proteasome inhibitor N-benzyloxycarbonyl-Ile-Glu-(O-t-butyl)-Ala-leucinal (PSI) or corresponding volume of vehicle i.p. 2 h before sham-operation or induction of sepsis by cecal ligation and puncture. The sepsis-induced increase in total and myofibrillar muscle protein breakdown was inhibited in rats treated in vivo with PSI and a maximal effect was seen following 15 mg/kg of the proteasome inhibitor. Results from in vitro experiments in which incubated muscles were treated with 100 microM PSI suggest that the drug has a direct effect on muscle and that the effect is specific for the proteasome. The results are important because they suggest that it may be possible to prevent or improve the cachectic response in skeletal muscle during sepsis by treatment with a proteasome inhibitor.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Fischer D,Gang G,Pritts T,Hasselgren PO

doi

10.1006/bbrc.2000.2398

subject

Has Abstract

pub_date

2000-04-02 00:00:00

pages

215-21

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(00)92398-2

journal_volume

270

pub_type

杂志文章

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