Phorbol ester-induced protein kinase C translocation and lysosomal enzyme release in normal and cystic fibrosis fibroblasts

• Published in: FEBS letters Vol. 229; no. 1; pp. 161 - 166
• Main Authors: Hermelin, B., Cherqui, G., Bertrand, F., Wicek, D., Paul, A., Garcia, I., Picard, J.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 29.02.1988; Elsevier
• Subjects: 4α-phorbol 12,13-didecanoate; 4αPDD; 4β-phorbol 12β-myristate 13α-acetate; Acetylglucosaminidase - metabolism; Biological and medical sciences; bovine serum albumin; BSA; Cystic fibrosis; Cystic Fibrosis - enzymology; DMEM; Dose-Response Relationship, Drug; Dulbecco's modified Eagle's medium; Fibroblasts - enzymology; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Lysosomal enzyme release; Lysosomes - enzymology; Medical sciences; methylumbelliferyl; MUB; Other diseases. Semiology; PBS; phenylmethylsulfonyl fluoride; Phorbol ester; Phorbol Esters - pharmacology; phosphate-buffered saline; phosphatidylserine; PKC; PMA; PMSF; Protein kinase C; Protein Kinase C - metabolism; Skin fibroblast; Tetradecanoylphorbol Acetate - pharmacology; Time Factors; PBS; Protein kinase C; CF; PS; PMA; Phorbol ester; Cystic fibrosis; PKC; Skin fibroblast; BSA; DMEM; PMSF; Lysosomal enzyme release; 4αPDD; MUB; Human; Pathology; Mucoviscidosis; Enzymatic activity; Enzyme; Lysosome; Digestive diseases; Skin; Child; Fibroblast
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(88)80818-4

The ability of the tumor-promoting phorbol ester 4β-phorbol 12β-myristate 13α-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 β- N-acetylglucosaminidase release. In contrast, the inactive phorbol ester 4α-phorbol 12,13-didecanoate (4αPDD) proved ineffective in inducing PKC translocation and β- 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.