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Titolo:
The CFTR-mediated protein secretion defect: pharmacological correction
Autore:
McPherson, MA; Pereira, MMC; Russell, D; McNeilly, CM; Morris, RM; Stratford, FLL; Dormer, RL;
Indirizzi:
Univ Wales Coll Med, Dept Med Biochem, Cardiff CF14 4XN, S Glam, Wales Univ Wales Coll Med Cardiff S Glam Wales CF14 4XN CF14 4XN, S Glam, Wales
Titolo Testata:
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
, volume: 443, anno: 2001, supplemento:, 1
pagine: S121 - S126
SICI:
0031-6768(2001)443:<S121:TCPSDP>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSMEMBRANE CONDUCTANCE REGULATOR; BETA-ADRENERGIC STIMULATION; RAT SUBMANDIBULAR ACINI; CYSTIC-FIBROSIS; MUCIN SECRETION; MUTATION; ANTIBODY; GLANDS; CELLS; A(1);
Keywords:
cystic fibrosis transmembrane conductance; regulator; protein secretion; methylxanthines; exocrine glands; mucin; cyclic AMP; cystic fibrosis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
21
Recensione:
Indirizzi per estratti:
Indirizzo: McPherson, MA Univ Wales Coll Med, Dept Med Biochem, Heath Pk, Cardiff CF14 4XN, S Glam,Wales Univ Wales Coll Med Heath Pk Cardiff S Glam Wales CF14 4XN s
Citazione:
M.A. McPherson et al., "The CFTR-mediated protein secretion defect: pharmacological correction", PFLUG ARCH, 443, 2001, pp. S121-S126

Abstract

The cystic fibrosis transmembrane conductance regulator (CFTR) mediates secretion of mucins and serous proteins. The aim was to correct pharmacologically the CFTR defect in protein secretion in airway gland cells and so to correct the viscous mucous secretions in cystic fibrosis (CF) airways and lungs. The strategies tested included direct activation of CFTR, bypass of CFTR-mediated protein secretion and movement of the mutated form of CFTR (DeltaF(508)-CFTR) to the cell membrane. Compounds related to 3-isobutyl-1-maethyl-xanthine (IBMX), including a selective type-IV phosphodiesterase inhibitor and the adenosine receptor antagonists 8-cyclopentyltheophylline (CPT) and 8-cyclopentyl-1,3-dipropylxanthine (CPX), corrected the defective beta -adrenergic stimulation of mucin secretion in CFTR antibody-inhibited submandibular gland cells. CPT also corrected lactoferrin secretion in DeltaF(508)/DeltaF(508)-CFTR nasal gland cells. The data suggest that correction of CFTR protein secretion activity is not mediated by excessive increase in cyclic AMP, involves direct interaction with CFTR but does not require increase in CFTR Cl- channel activity. Regulated glycoprotein secretion was characterised in the airway gland cell line Calu-3 to investigate whether a CFTRbypass is present. Studies of DeltaF(508)-CFTR trafficking using confocal imaging showed that some DeltaF(508)-CFTR colocalised with the apical membrane protein CD59; however a large amount was mislocalised within the cell. The results showing pharmacological correction of the defective CFTR-mediated protein secretion afford promise for the development of a rational drug therapy for CF patients.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/07/20 alle ore 06:30:14