Glucosamine induces translocation of protein kinase C isoenzymes in mesangial cells.
Activation of protein kinase C (PKC) has been implicated in the high glucose-induced stimulation of matrix protein production in mesangial cells. Since we have found (Kolm-Litty et al., 1998) that glucosamine, similar to the PKC activator phorbol myristate acetate (PMA), mimicks high glucose-induced TGF-beta1 overexpression and subsequent matrix overproduction, the action of these agents on the translocation of PKC isoenzymes was studied in cultured mesangial cells. Exposure to 12 mM glucosamine resulted in rapid and specific translocation of PKC-isoenzymes in mesangial cells i.e. glucosamine caused an increased and sustained translocation of PKC-alpha, -beta and -epsilon while PKC-zeta was essentially unaffected. Comparison with PMA-induced translocation exhibited distinct differences. Exposure to high glucose concentrations of mesangial cells induced translocation of PKC-beta and down-regulation of PKC-epsilon while PKC-alpha and -zeta were essentially unaltered. Presence of azaserine an inhibitor of glutamine: fructose-6-phosphate amidotransferase, the key enzyme of the hexosamine pathway, attenuated the high glucose-induced effects on the membrane fraction of PKC-beta. Our results indicate that i) glucosamine is a potent stimulator of PKC-translocation exhibiting an isoenzyme specific translocation kinetic which is different from PMA-induced PKC-isoenzyme translocation ii) the hexosamine pathway may be possibly involved in the high glucose-induced activation of PKC.
Kolm-Litty
V
V
Institut für Diabetesforschung, Krankenhaus München-Schwabing, München, Germany.
Tippmer
S
S
Häring
H U
HU
Schleicher
E
E
D000818:Animals; D001377:Azaserine / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000187:drug effects / Q000201:enzymology*; D005944:Glucosamine / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D011493:Protein Kinase C / Q000378:metabolism*; D013552:Swine; D013755:Tetradecanoylphorbol Acetate
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D001377:Azaserine; D011493:Protein Kinase C; D005947:Glucose; D005944:Glucosamine; D013755:Tetradecanoylphorbol Acetate