Mechanism of induction of muscle protein degradation by angiotensin II

Steve T. Russell, Stacey M. Wyke, Michael J. Tisdale*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Angiotensin I and II have been shown to directly induce protein degradation in skeletal muscle through an increased activity and expression of the ubiquitin-proteasome proteolytic pathway. This investigation determines the role of the nuclear transcription factor nuclear factor-κB (NF-κB) in this process. Using murine myotubes as a surrogate model system both angiotensin I and II were found to induce activation of protein kinase C (PKC), with a parabolic dose-response curve similar to the induction of total protein degradation. Activation of PKC was required for the induction of proteasome expression, since calphostin C, a highly specific inhibitor of PKC, attenuated both the increase in total protein degradation and in proteasome expression and functional activity increased by angiotensin II. PKC is known to activate I-κB kinase (IKK), which is responsible for the phosphorylation and subsequent degradation of I-κB. Both angiotensin I and II induced an early decrease in cytoplasmic I-κB levels followed by nuclear accumulation of NF-κB. Using an NF-κB luciferase construct this was shown to increase transcriptional activation of NF-κB regulated genes. Maximal luciferase expression was seen at the same concentrations of angiotensin I/II as those inducing protein degradation. Total protein degradation induced by both angiotensin I and II was attenuated by resveratrol, which prevented nuclear accumulation of NF-κB, confirming that activation of NF-κB was responsible for the increased protein degradation. These results suggest that induction of proteasome expression by angiotensin I/II involves a signalling pathway involving PKC and NF-κB. © 2005 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)1087-1096
Number of pages10
JournalCellular Signalling
Volume18
Issue number7
DOIs
Publication statusPublished - Jul 2006

Fingerprint

Muscle Proteins
Angiotensin I
Angiotensin II
Proteolysis
Protein Kinase C
Proteasome Endopeptidase Complex
Luciferases
Skeletal Muscle Fibers
Ubiquitin
Transcriptional Activation
Skeletal Muscle
Transcription Factors
Phosphotransferases
Phosphorylation
Genes

Keywords

  • angiotensin I/II
  • NF-κB
  • protein degradation
  • protein kinase C

Cite this

Russell, Steve T. ; Wyke, Stacey M. ; Tisdale, Michael J. / Mechanism of induction of muscle protein degradation by angiotensin II. In: Cellular Signalling. 2006 ; Vol. 18, No. 7. pp. 1087-1096.
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Mechanism of induction of muscle protein degradation by angiotensin II. / Russell, Steve T.; Wyke, Stacey M.; Tisdale, Michael J.

In: Cellular Signalling, Vol. 18, No. 7, 07.2006, p. 1087-1096.

Research output: Contribution to journalArticle

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