Attenuation of muscle atrophy by an N-terminal peptide of the receptor for proteolysis-inducing factor (PIF)

Kamran Mirza, Stacey M. Wyke, Michael Tisdale

Research output: Contribution to journalArticle

Abstract

Background: Atrophy of skeletal muscle in cancer cachexia has been attributed to a tumour-produced highly glycosylated peptide called proteolysis-inducing factor (PIF). The action of PIF is mediated through a high-affinity membrane receptor in muscle. This study investigates the ability of peptides derived from the 20 N-terminal amino acids of the receptor to neutralise PIF action both in vitro and in vivo.

Methods: Proteolysis-inducing factor was purified from the MAC16 tumour using an initial pronase digestion, followed by binding on DEAE cellulose, and the pronase was inactivated by heating to 80°C, before purification of the PIF using affinity chromatography. In vitro studies were carried out using C2C12 murine myotubes, while in vivo studies employed mice bearing the cachexia-inducing MAC16 tumour.

Results: The process resulted in almost a 23?000-fold purification of PIF, but with a recovery of only 0.004%. Both the D- and L-forms of the 20mer peptide attenuated PIF-induced protein degradation in vitro through the ubiquitin-proteosome proteolytic pathway and increased expression of myosin. In vivo studies showed that neither the D- nor the L-peptides significantly attenuated weight loss, although the D-peptide did show a tendency to increase lean body mass.

Conclusion: These results suggest that the peptides may be too hydrophilic to be used as therapeutic agents, but confirm the importance of the receptor in the action of the PIF on muscle protein degradation.
LanguageEnglish
Pages83-88
Number of pages5
JournalBritish Journal of Cancer
Volume105
Issue number1
DOIs
Publication statusPublished - 14 Jun 2011

Fingerprint

Peptide Receptors
Muscular Atrophy
Proteolysis
Pronase
Cachexia
Peptides
Muscle Neoplasms
Amino Acid Receptors
L Forms
DEAE-Cellulose
Neoplasms
Muscle Proteins
Skeletal Muscle Fibers
Myosins
Ubiquitin
Affinity Chromatography
Heating
Atrophy
Weight Loss
Digestion

Keywords

  • proteolysis-inducing factor
  • cancer cachexia
  • PIF receptor
  • PIF
  • muscle protein degradation

Cite this

Mirza, Kamran ; Wyke, Stacey M. ; Tisdale, Michael. / Attenuation of muscle atrophy by an N-terminal peptide of the receptor for proteolysis-inducing factor (PIF). In: British Journal of Cancer. 2011 ; Vol. 105, No. 1. pp. 83-88.
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abstract = "Background: Atrophy of skeletal muscle in cancer cachexia has been attributed to a tumour-produced highly glycosylated peptide called proteolysis-inducing factor (PIF). The action of PIF is mediated through a high-affinity membrane receptor in muscle. This study investigates the ability of peptides derived from the 20 N-terminal amino acids of the receptor to neutralise PIF action both in vitro and in vivo.Methods: Proteolysis-inducing factor was purified from the MAC16 tumour using an initial pronase digestion, followed by binding on DEAE cellulose, and the pronase was inactivated by heating to 80°C, before purification of the PIF using affinity chromatography. In vitro studies were carried out using C2C12 murine myotubes, while in vivo studies employed mice bearing the cachexia-inducing MAC16 tumour.Results: The process resulted in almost a 23?000-fold purification of PIF, but with a recovery of only 0.004{\%}. Both the D- and L-forms of the 20mer peptide attenuated PIF-induced protein degradation in vitro through the ubiquitin-proteosome proteolytic pathway and increased expression of myosin. In vivo studies showed that neither the D- nor the L-peptides significantly attenuated weight loss, although the D-peptide did show a tendency to increase lean body mass.Conclusion: These results suggest that the peptides may be too hydrophilic to be used as therapeutic agents, but confirm the importance of the receptor in the action of the PIF on muscle protein degradation.",
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Attenuation of muscle atrophy by an N-terminal peptide of the receptor for proteolysis-inducing factor (PIF). / Mirza, Kamran; Wyke, Stacey M.; Tisdale, Michael.

In: British Journal of Cancer, Vol. 105, No. 1, 14.06.2011, p. 83-88.

Research output: Contribution to journalArticle

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