Role of Ca2+ in proteolysis-inducing factor (PIF)-induced atrophy of skeletal muscle

Kamran Mirza, Michael Tisdale

Research output: Contribution to journalArticle

Abstract

Proteolysis-inducing factor (PIF) induces muscle loss in cancer cachexia through a high affinity membrane bound receptor. This study investigates the mechanism by which the PIF receptor communicates to intracellular signalling pathways. C2C12 murine myoblasts were used as a model using PIF purified from MAC16 tumours. Calcium imaging was determined using fura-4-acetoxymethyl ester (Fura-4-AM). PIF induced a rapid rise in Ca2 +i, which was completely attenuated by a anti-receptor antibody, or peptides representing 20 mers of the N-terminus of the PIF receptor. Other agents catabolic for skeletal muscle including angiotensin II (AngII) tumour necrosis factor-a (TNF-a) and lipopolysaccharide (LPS) also induced a rise in Ca2 +i, but this was not attenuated by anti-PIF-receptor antibody. The rise in Ca2 +i induced by PIF and AngII was completely attenuated by the Zn2 + chelator D-myo-inositol-1,2,6-triphosphate, and this was reversed by administration of exogenous Zn2 +. The Ca2 +i rise induced by PIF was independent of the presence of extracellular Ca2 +, and attenuated by the Ca2 + pump inhibitor thapsigargin, suggesting that the Ca2 +i rise was due to release from intracellular stores. This rise in Ca2 +i induced by PIF was attenuated by both the phospholipase C inhibitor U73122 and 2-APB, an inhibitor of the inositol 1,4,5-triphosphate receptor, suggesting the involvement of a G-protein. Binding of the PIF to its receptor in skeletal muscle triggers a rise in Ca2 +i, which initiates a signalling cascade leading to a depression in protein synthesis, and an increase in protein degradation.
LanguageEnglish
Pages2118–2122
Number of pages4
JournalCellular Signalling
Volume24
Issue number11
DOIs
Publication statusPublished - Nov 2011

Fingerprint

Proteolysis
Atrophy
Skeletal Muscle
Angiotensin II
Inositol 1,4,5-Trisphosphate Receptors
Cachexia
Thapsigargin
Myoblasts
Type C Phospholipases
Prothrombin
Chelating Agents
GTP-Binding Proteins
Lipopolysaccharides
Anti-Idiotypic Antibodies
Neoplasms
Esters
Tumor Necrosis Factor-alpha
Calcium
Muscles
Peptides

Keywords

  • proteolysis-inducing factor
  • PIF
  • PIF-receptor
  • Ca2 + signalling
  • cancer cachexia

Cite this

Mirza, Kamran ; Tisdale, Michael. / Role of Ca2+ in proteolysis-inducing factor (PIF)-induced atrophy of skeletal muscle. In: Cellular Signalling. 2011 ; Vol. 24, No. 11. pp. 2118–2122.
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Role of Ca2+ in proteolysis-inducing factor (PIF)-induced atrophy of skeletal muscle. / Mirza, Kamran; Tisdale, Michael.

In: Cellular Signalling, Vol. 24, No. 11, 11.2011, p. 2118–2122.

Research output: Contribution to journalArticle

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