GLUCOSAMINE INDUCES TRANSLOCATION OF PROTEIN-KINASE-C ISOENZYMES IN MESANGIAL CELLS

Activation of protein kinase C (PKC) has been implicated in the high g lucose-induced stimulation of matrix protein production in mesangial c ells. 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-beta 1 overexpression and subsequent matrix o verproduction, 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-isoenz ymes in mesangial cells i.e. glucosamine caused an increased and susta ined translocation of PKC-alpha, -beta and -epsilon while PKC-zeta was essentially unaffected. Comparison with PMA-induced translocation exh ibited distinct differences. Exposure to high glucose concentrations o f mesangial cells induced translocation of PKC-beta and down-regulatio n 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, attenuate d the high glucose-induced effects on the membrane fraction of PKC-bet a. Our results indicate that i) glucosamine is a potent stimulator of PKC-translocation exhibiting an isoenzyme specific translocation kinet ic which is different from PMA-induced PKC-isoenzyme translocation ii) the hexosamine pathway may be possibly involved in the high glucose-i nduced activation of PKC.