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Journal of Physiology and Biochemistry

, Volume 66, Issue 4, pp 311–319 | Cite as

Effects of β-hydroxy-β-methylbutyrate treatment in different types of skeletal muscle of intact and septic rats

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

Abstract

β-Hydroxy-β-methylbutyrate (HMB) is a leucine metabolite that may have a positive effect in protein catabolic conditions. Therefore, we hypothesized that HMB treatment could attenuate the sepsis-induced protein catabolic state. The aims of our study were to elucidate the effect of HMB in healthy and septic animals and to evaluate the differences in the action of HMB in different muscle types. Intact and septic (5 mg endotoxin/kg i.p.) rats were administered with HMB (0.5 g/kg/day) or saline. After 24 h, extensor digitorum longus (EDL) and soleus (SOL) muscles were isolated and used for determination of total and myofibrillar proteolysis, protein synthesis, leucine oxidation, activity of cathepsins B and L, chymotrypsin-like activity, and expression of α-subunits of proteasome. Our results indicate that the catabolic state induced by the endotoxin treatment was caused both by increase in protein breakdown (due to activation of proteasome system) and by attenuation of protein synthesis. The EDL (muscle composed of white, fast-twitch fibers) was more susceptible to these changes than the SOL (muscle composed of red, slow-twitch fibers). The HMB treatment had no effect in healthy animals but counteracted the changes in septic animals. The action of HMB was mediated by attenuation of proteasome activity and protein breakdown, not by stimulation of protein synthesis. More pronounced effect of the HMB treatment on myofibrillar proteolysis was observed in the SOL.

Keywords

Proteasome Inflammation Amino acid Protein metabolism Skeletal muscle 

Abbreviations

3-MH

3-Methylhistidine

AMC

7-Amino-4-methylcoumarin

BCAA

Branched-chain amino acids (leucine isoleucine and valine)

CTLA

Chymotrypsin-like activity of proteasome

EDL

Musculus extensor digitorum longus

HMB

β-Hydroxy-β-methylbutyrate

MuRF-1

Muscle RING finger protein 1

NF-κB

Nuclear factor κB

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

Acknowledgment

This study was supported by the Research Project of the Czech Ministry of Education, Youth, and Sports MSM 0021620820 and by the Grant of Charles University Grant Agency 7322/2007.

Our thanks go to J. A. Rathmacher from Metabolic Technologies for kind donation of HMB, to A. Mehta and M. Stanglova for language correction, and to R. Rysava and H. Buzkova for the technical support.

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Copyright information

© University of Navarra 2010

Authors and Affiliations

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

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