Calpain inhibition promotes the rescue of F(508)del-CFTR in PBMC from cystic fibrosis patients.

A basal calpain activity promotes the limited proteolysis of wild type (WT) cystic fibrosis conductance regulator (CFTR), inducing the internalization of the split channel. This process contributes to the regulation in the level of the active CFTR at the plasma membranes. In peripheral blood mononuc...

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Autores principales:	Monica Averna, Marco Pedrazzi, Laura Minicucci, Roberta De Tullio, Federico Cresta, Franca Salamino, Sandro Pontremoli, Edon Melloni
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dd6fb6db9bbc4c0bbc38fc5fce5e4761
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spelling	oai:doaj.org-article:dd6fb6db9bbc4c0bbc38fc5fce5e47612021-11-18T07:41:52ZCalpain inhibition promotes the rescue of F(508)del-CFTR in PBMC from cystic fibrosis patients.1932-620310.1371/journal.pone.0066089https://doaj.org/article/dd6fb6db9bbc4c0bbc38fc5fce5e47612013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23785472/?tool=EBIhttps://doaj.org/toc/1932-6203A basal calpain activity promotes the limited proteolysis of wild type (WT) cystic fibrosis conductance regulator (CFTR), inducing the internalization of the split channel. This process contributes to the regulation in the level of the active CFTR at the plasma membranes. In peripheral blood mononuclear cells (PBMC) from 16 healthy donors, the inhibition of calpain activity induces a 3-fold increase in the amount of active WT CFTR at the plasma membranes. Instead, in PBMC from cystic fibrosis (CF) patients, calpain activity is expressed at aberrant levels causing the massive removal of F(508)del-CFTR from the cell surface. In these patients, the inhibition of such abnormal proteolysis rescues physiological amounts of active mutated CFTR in 90% of the patients (25 over 28). The recovery of functional F(508)del-CFTR at the physiological location, in cells treated with a synthetic calpain inhibitor, indicates that F(508)del-CFTR folding, maturation, and trafficking operate in CF-PBMC at significant rate. Thus, an increase in the basal calpain activity seems primarily involved in the CFTR defect observed in various CF cells. Furthermore, in CF-PBMC the recovery of the scaffolding protein Na(+)/H(+) exchanger regulatory factor 1 (NHERF-1), occurring following inhibition of the aberrant calpain activity, can contribute to rescue CFTR-functional clusters.Monica AvernaMarco PedrazziLaura MinicucciRoberta De TullioFederico CrestaFranca SalaminoSandro PontremoliEdon MelloniPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e66089 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Monica Averna Marco Pedrazzi Laura Minicucci Roberta De Tullio Federico Cresta Franca Salamino Sandro Pontremoli Edon Melloni Calpain inhibition promotes the rescue of F(508)del-CFTR in PBMC from cystic fibrosis patients.
description	A basal calpain activity promotes the limited proteolysis of wild type (WT) cystic fibrosis conductance regulator (CFTR), inducing the internalization of the split channel. This process contributes to the regulation in the level of the active CFTR at the plasma membranes. In peripheral blood mononuclear cells (PBMC) from 16 healthy donors, the inhibition of calpain activity induces a 3-fold increase in the amount of active WT CFTR at the plasma membranes. Instead, in PBMC from cystic fibrosis (CF) patients, calpain activity is expressed at aberrant levels causing the massive removal of F(508)del-CFTR from the cell surface. In these patients, the inhibition of such abnormal proteolysis rescues physiological amounts of active mutated CFTR in 90% of the patients (25 over 28). The recovery of functional F(508)del-CFTR at the physiological location, in cells treated with a synthetic calpain inhibitor, indicates that F(508)del-CFTR folding, maturation, and trafficking operate in CF-PBMC at significant rate. Thus, an increase in the basal calpain activity seems primarily involved in the CFTR defect observed in various CF cells. Furthermore, in CF-PBMC the recovery of the scaffolding protein Na(+)/H(+) exchanger regulatory factor 1 (NHERF-1), occurring following inhibition of the aberrant calpain activity, can contribute to rescue CFTR-functional clusters.
format	article
author	Monica Averna Marco Pedrazzi Laura Minicucci Roberta De Tullio Federico Cresta Franca Salamino Sandro Pontremoli Edon Melloni
author_facet	Monica Averna Marco Pedrazzi Laura Minicucci Roberta De Tullio Federico Cresta Franca Salamino Sandro Pontremoli Edon Melloni
author_sort	Monica Averna
title	Calpain inhibition promotes the rescue of F(508)del-CFTR in PBMC from cystic fibrosis patients.
title_short	Calpain inhibition promotes the rescue of F(508)del-CFTR in PBMC from cystic fibrosis patients.
title_full	Calpain inhibition promotes the rescue of F(508)del-CFTR in PBMC from cystic fibrosis patients.
title_fullStr	Calpain inhibition promotes the rescue of F(508)del-CFTR in PBMC from cystic fibrosis patients.
title_full_unstemmed	Calpain inhibition promotes the rescue of F(508)del-CFTR in PBMC from cystic fibrosis patients.
title_sort	calpain inhibition promotes the rescue of f(508)del-cftr in pbmc from cystic fibrosis patients.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/dd6fb6db9bbc4c0bbc38fc5fce5e4761
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Calpain inhibition promotes the rescue of F(508)del-CFTR in PBMC from cystic fibrosis patients.

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