BILIRUBIN INHIBITS PROTEIN-KINASE-C ACTIVITY AND PROTEIN-KINASE C-MEDIATED PHOSPHORYLATION OF ENDOGENOUS SUBSTRATES IN HUMAN SKIN FIBROBLASTS

Authors
Citation
Y. Amit et A. Boneh, BILIRUBIN INHIBITS PROTEIN-KINASE-C ACTIVITY AND PROTEIN-KINASE C-MEDIATED PHOSPHORYLATION OF ENDOGENOUS SUBSTRATES IN HUMAN SKIN FIBROBLASTS, Clinica chimica acta, 223(1-2), 1993, pp. 103-111
Citations number
15
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Chemistry Medicinal
Journal title
ISSN journal
0009-8981
Volume
223
Issue
1-2
Year of publication
1993
Pages
103 - 111
Database
ISI
SICI code
0009-8981(1993)223:1-2<103:BIPAAP>2.0.ZU;2-9
Abstract
The primary target and molecular basis of bilirubin toxicity to cellul ar function are not known. We have studied the effect of bilirubin on protein kinase C activity in subcellular fractions of human skin fibro blasts and on protein kinase C-mediated phosphorylation of endogenous substrates. Bilirubin inhibited the kinase activity in a concentration -dependent manner: a 50% inhibition was achieved by 45 mu mol/l in the homogenate and 75 mu mol/l in both the cytosolic and membranous fract ions. Inhibition of protein kinase C activity by bilirubin was reverse d by increasing the concentrations of activating lipids in both the cy tosolic and membranous fractions. Bilirubin-induced inhibition of phos phorylation of endogenous proteins, in both fractions, was noted in th e presence of calcium and the activating lipids, but not in the absenc e of the activators. This inhibition may play a role in the pathogenes is of bilirubin toxicity.