ABNORMALITIES IN PROTEIN-KINASE-C AND MAP KINASE CASCADE IN MESANGIALCELLS CULTURED UNDER HIGH GLUCOSE CONDITIONS

In order to clarify the mechanism of mesangial cell dysfunction in dia betes, we examined the activities of protein kinase C (PKC) and mitoge n-activated protein kinase (MAPK), important kinases in various cellul ar functions, and also evaluated the isoenzymes of PKC in mesangial ce lls cultured under high glucose conditions, Exposure of cells to high concentrations (27.8 mM) of glucose for 5 days resulted in a significa nt elevation of PKC activities in the membrane fraction. MAPK was also activated in cells cultured under high glucose conditions. Of the PKC isoenzymes, the levels of PKC alpha and zeta were significantly incre ased in the membrane fraction after 5 days of exposure to high concent rations of glucose. These results indicate that the translocation of P KC alpha and zeta and the activation of MAPK under high glucose condit ions might be underlying mechanisms of the functional. disturbance of mesangial cells in diabetes.