Downregulation of ubiquitin-dependent proteolysis by eicosapentaenoic acid in acute starvation

A.S. Whitehouse, Michael J. Tisdale

Research output: Contribution to journalArticle

Abstract

A number of acute wasting conditions are associated with an upregulation of the ubiquitin-proteasome system in skeletal muscle. Eicosapentaenoic acid (EPA) is effective in attenuating the increased protein catabolism in muscle in cancer cachexia, possibly due to inhibition of 15-hydroxyeicosatetraenoic acid (15-HETE) formation. To determine if a similar pathway is involved in other catabolic conditions, the effect of EPA on muscle protein degradation and activation of the ubiquitin-proteasome pathway has been determined during acute fasting in mice. When compared with a vehicle control group (olive oil) there was a significant decrease in proteolysis of the soleus muscles of mice treated with EPA after starvation for 24 h, together with an attenuation of the proteasome 'chymotryptic-like' enzyme activity and the induction of the expression of the 20S proteasome α-subunits, the 19S regulator and p42, an ATPase subunit of the 19S regulator in gastrocnemius muscle, and the ubiquitin-conjugating enzyme E214k. The effect was not shown with the related (n-3) fatty acid docosahexaenoic acid (DHA) or with linoleic acid. However, 2,3,5trimethyl-6-(3-pyridylmethyl)1,4-benzoquinone (CV-6504), an inhibitor of 5-, 12- and 15-lipoxygenases also attenuated muscle protein catabolism, proteasome 'chymotryptic-like' enzyme activity and expression of proteasome 20S α-subunits in soleus muscles from acute fasted mice. These results suggest that protein catabolism in starvation and cancer cachexia is mediated through a common pathway, which is inhibited by EPA and is likely to involve a lipoxygenase metabolite as a signal transducer. © 2001 Academic Press.

Original languageEnglish
Pages (from-to)598-602
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume285
Issue number3
DOIs
Publication statusPublished - 14 Oct 2001

Fingerprint

Proteolysis
Eicosapentaenoic Acid
Proteasome Endopeptidase Complex
Ubiquitin
Starvation
Down-Regulation
Muscle
Skeletal Muscle
Cachexia
Muscle Proteins
Enzyme activity
Muscle Neoplasms
Ubiquitin-Conjugating Enzymes
Hydroxyeicosatetraenoic Acids
Enzyme Induction
Lipoxygenase
Docosahexaenoic Acids
Omega-3 Fatty Acids
Linoleic Acid
Metabolites

Keywords

  • 15-HETE
  • EPA
  • starvation
  • ubiquitin-proteasome proteolysis

Cite this

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abstract = "A number of acute wasting conditions are associated with an upregulation of the ubiquitin-proteasome system in skeletal muscle. Eicosapentaenoic acid (EPA) is effective in attenuating the increased protein catabolism in muscle in cancer cachexia, possibly due to inhibition of 15-hydroxyeicosatetraenoic acid (15-HETE) formation. To determine if a similar pathway is involved in other catabolic conditions, the effect of EPA on muscle protein degradation and activation of the ubiquitin-proteasome pathway has been determined during acute fasting in mice. When compared with a vehicle control group (olive oil) there was a significant decrease in proteolysis of the soleus muscles of mice treated with EPA after starvation for 24 h, together with an attenuation of the proteasome 'chymotryptic-like' enzyme activity and the induction of the expression of the 20S proteasome α-subunits, the 19S regulator and p42, an ATPase subunit of the 19S regulator in gastrocnemius muscle, and the ubiquitin-conjugating enzyme E214k. The effect was not shown with the related (n-3) fatty acid docosahexaenoic acid (DHA) or with linoleic acid. However, 2,3,5trimethyl-6-(3-pyridylmethyl)1,4-benzoquinone (CV-6504), an inhibitor of 5-, 12- and 15-lipoxygenases also attenuated muscle protein catabolism, proteasome 'chymotryptic-like' enzyme activity and expression of proteasome 20S α-subunits in soleus muscles from acute fasted mice. These results suggest that protein catabolism in starvation and cancer cachexia is mediated through a common pathway, which is inhibited by EPA and is likely to involve a lipoxygenase metabolite as a signal transducer. {\circledC} 2001 Academic Press.",
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Downregulation of ubiquitin-dependent proteolysis by eicosapentaenoic acid in acute starvation. / Whitehouse, A.S.; Tisdale, Michael J.

In: Biochemical and Biophysical Research Communications, Vol. 285, No. 3, 14.10.2001, p. 598-602.

Research output: Contribution to journalArticle

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