Glucosamine induces translocation of Protein kinase C isoenzymes in mesangial cells

 

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Summary

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-βl overexpression and subsequent matrix overproduction, the action of these agents on the translocation of PKC iso-enzymes 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−α, −β and −ε while PKC−ζ was essentially unaffected. Comparison with PMA-in-duced translocation exhibited distinct differences. Exposure to high glucose concentrations of mesangial cells induced translocation of PKC−β and down-regulation of PKC−ε while PKC−α and −ζ 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−β. 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.