Journal of Physiology and Biochemistry

, Volume 68, Issue 3, pp 385–395 | Cite as

The dose-dependent effects of endotoxin on protein metabolism in two types of rat skeletal muscle

  • Miroslav Kovarik
  • Tomas Muthny
  • Ludek Sispera
  • Milan Holecek
Original Paper

Abstract

Endotoxin administration is frequently used as a model of systemic inflammatory response which is considered the important pathogenetic factor in muscle wasting development in severe illness, such as sepsis, cancer, injury, AIDS and others. The main purpose of this study was determining the effect of various doses of endotoxin on protein and amino acid metabolism in two types of rat skeletal muscle. Sepsis was induced by intraperitoneal administration of endotoxin in a dose of 1, 3 and 5 mg/kg body weight (bw); control animals received a corresponding volume of the saline solution. After 24 h, extensor digitorum longus (EDL) and soleus (SOL) muscles were isolated and used for determination of total and myofibrillar proteolysis, protein synthesis, activity of cathepsins B and L, chymotrypsin-like activity of proteasome and amino acid release. The endotoxemia induced the body weight loss, the rise of total cholesterol and triglyceride plasma concentration and the protein catabolic state in skeletal muscle, which was caused by a higher increase in protein breakdown (due to activation of the proteasome system) than protein synthesis. The more significant effect of endotoxin was seen in EDL than SOL. The dose of 5 mg of endotoxin/kg bw induced the most significant changes in parameters of the protein and amino acid metabolism measured and could be therefore considered appropriate for studies of protein catabolism in young rat skeletal muscle at 24 h after endotoxin treatment.

Keywords

Endotoxin Skeletal muscle Protein metabolism Proteasome 

Abbreviations

3-MH

3-Methylhistidine (N-τ-methylhistidine)

AMC

7-Amino-4-methylcoumarin

bw

Body weight

CTLA

Chymotrypsin-like activity of proteasome

EDL

Musculus extensor digitorum longus

SOL

Musculus soleus

Suc-LLVY-MCA

N-Succinyl-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin

Z-FA-MCA

Z-Phe-Arg 7-amido-4-methylcoumarin hydrochloride

Z-FF-FMK

Z-Phe-Phe-fluoromethyl ketone

Notes

Acknowledgements

This study was supported by the research project of the Czech Ministry of Education, Youth, and Sports MSM 0021620820.

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Copyright information

© University of Navarra 2012

Authors and Affiliations

  • Miroslav Kovarik
    • 1
    • 2
  • Tomas Muthny
    • 1
  • Ludek Sispera
    • 1
  • Milan Holecek
    • 1
  1. 1.Department of Physiology, Faculty of MedicineCharles UniversityHradec KraloveCzech Republic
  2. 2.Department of Biological and Medical Sciences, Faculty of PharmacyCharles UniversityHradec KraloveCzech Republic

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