Evidence for alteration of calpain/calpastatin system in PBMC of cystic fibrosis patients

Monica Averna, Roberto Stifanese, Roberta De Tullio, Laura Minicucci, Federico Cresta, Serena Palena, Franca Salamino, Sandro Pontremoli, Edon Melloni

Research output: Contribution to journalArticlepeer-review

Abstract

We are here reporting that in peripheral blood mononuclear cells (PBMC) of patients homozygous for F508del-CFTR the calpain-calpastatin system undergoes a profound alteration. In fact, calpain basal activity, almost undetectable in control PBMC, becomes measurable at a significant extent in cells from cystic fibrosis (CF) patients, also due to a 40-60% decrease in both calpastatin protein and inhibitory activity. Constitutive protease activation in CF patients' cells induces a large accumulation of the mutated cystic fibrosis transmembrane conductance regulator (CFTR) in the 100kD+70kD split forms as well as a degradation of proteins associated to the CFTR complex. Specifically, the scaffolding protein Na +/H + exchanger 3 regulatory factor-1 (NHERF-1) is converted in two distinct fragments showing masses of 35kD and 20kD, being however the latter form the most represented one, thereby indicating that in CF-PBMC the CFTR complex undergoes a large disorganization. In conclusion, our observations are providing new information on the role of calpain in the regulation of plasma membrane ion conductance and provide additional evidence on the transition of this protease activity from a physiological to a pathological function.

Original languageEnglish
Pages (from-to)1649-1657
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1812
Issue number12
DOIs
Publication statusPublished - Dec 2011

Keywords

  • Ca -dependent proteolysis
  • Calpain
  • CFTR
  • Ezrin
  • F508del-CFTR
  • NHERF-1

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

Fingerprint Dive into the research topics of 'Evidence for alteration of calpain/calpastatin system in PBMC of cystic fibrosis patients'. Together they form a unique fingerprint.

Cite this