Tripeptidyl-peptidase II expression and activity are increased in skeletal muscle during sepsis

Curtis J. Wray, Birgitta Tomkinson, Bruce Robb, Per Olof Hasselgren

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Ubiquitin-proteasome-dependent protein degradation plays a central role in sepsis-induced muscle wasting. Because the proteasome degrades proteins into small peptides rather than free amino acids, it is likely that additional mechanisms downstream of the proteasome are involved in sepsis-induced muscle proteolysis. Recent studies suggest that the extralysosomal peptidase tripeptidyl-peptidase II (TPP II) degrades peptides generated by the proteasome. We hypothesized that TPP II expression and activity are increased in skeletal muscle during sepsis. Sepsis was induced in rats by cecal ligation and puncture. Control rats were sham-operated. TPP II activity was determined by using the specific substrate Ala-Ala-Phe-7-amido-4-methylcoumarin (AAF-AMC). TPP II protein and gene expression were determined by Western blot and real-time PCR, respectively. Sepsis resulted in increased activity and protein and gene expression of TPP II in extensor digitorum longus muscles. This result was blunted by the glucocorticoid receptor antagonist RU 38486, indicating that glucocorticoids participate in the upregulation of TPP II in skeletal muscle during sepsis. The results suggest that proteolytic mechanisms downstream of the proteasome may be important for the complete degradation of muscle proteins during sepsis.

Original languageEnglish (US)
Pages (from-to)41-47
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume296
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

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Proteasome Endopeptidase Complex
Muscle
Sepsis
Skeletal Muscle
Gene expression
Muscles
Proteolysis
Rat control
Degradation
Mifepristone
Peptides
Muscle Proteins
Gene Expression
Glucocorticoid Receptors
Proteins
Ubiquitin
Glucocorticoids
tripeptidyl-peptidase 2
Rats
Punctures

Keywords

  • Glucocorticoids
  • Muscle wasting
  • Proteasome
  • Ubiquitin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Tripeptidyl-peptidase II expression and activity are increased in skeletal muscle during sepsis. / Wray, Curtis J.; Tomkinson, Birgitta; Robb, Bruce; Hasselgren, Per Olof.

In: Biochemical and Biophysical Research Communications, Vol. 296, No. 1, 2002, p. 41-47.

Research output: Contribution to journalArticle

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