title: Phorbol ester-induced protein kinase C translocation and lysosomal enzyme release in normal and cystic fibrosis fibroblasts.
abstract: The ability of the tumor-promoting phorbol ester 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) to induce protein kinase C (PKC) translocation and lysosomal enzyme release was examined in skin fibroblasts from normal subjects and from patients with cystic fibrosis (CF). As compared to normal fibroblasts, those CF exhibited: (i) an increased sensitivity to the effect of PMA on the disappearance of PKC from cytosolic fractions as well as a greater and earlier recovery, in the membrane fraction, of the PKC activity lost in the cytosolic fraction; (ii) an earlier response to PMA for its effect on beta-N-acetylglucosaminidase release. In contrast, the inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD) proved ineffective in inducing PKC translocation and beta-N-acetylglucosaminidase release in both normal and CF fibroblasts. The data suggest a defect in the regulation of PKC activity in CF fibroblasts, which may lead to altered secretion.
authors.affiliation: Laboratoire de Biochimie, INSERM U 181, Faculté de Médecine Saint-Antoine, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Hermelin
authors.forename: G
authors.initials: G
authors.lastname: Cherqui
authors.forename: F
authors.initials: F
authors.lastname: Bertrand
authors.forename: D
authors.initials: D
authors.lastname: Wicek
authors.forename: A
authors.initials: A
authors.lastname: Paul
authors.forename: I
authors.initials: I
authors.lastname: Garcia
authors.forename: J
authors.initials: J
authors.lastname: Picard
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D003550:Cystic Fibrosis / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D008247:Lysosomes / Q000201:enzymology*; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
chemical_list: D010703:Phorbol Esters; D011493:Protein Kinase C; D000118:Acetylglucosaminidase; D013755:Tetradecanoylphorbol Acetate