MODULATION OF PROTEIN-KINASE-C BY HEAVY-METALS

Protein kinase C (PKC) regulates a variety of intracellular and extrac ellular signals across the neuronal membrane, PKC requires calcium and phospholipid, particularly phosphatidylserine (PS) for its activation . The data indicates that mercury (Hg), lead (Pb) and methyl mercury ( CH3Hg) in vitro inhibited the PKC activity at micromolar concentration s in a concentration-dependent manner with IC50 values of 1.5, 2.12 an d 0.22 mu M, respectively, The IC50 values indicate that CH3Hg was mor e potent in inhibiting the enzyme activity than Hg or Pb. The basal PK C activity was also inhibited by Pb or Hg. However, the PS-stimulated PKC activity was more sensitive to Pb or Hg than the basal enzyme, The phorbol ester binding to PKC was also found to be inhibited by microm olar concentrations of these metals in vitro. Hg and CH3Hg were more p otent inhibitors of phorbol ester binding than Pb. Dithiothreitol (DTT ), a dithiol, but not glutathione (GSH) a monothiol, protected the act ivities of both PS-stimulated and basal PKC from metal-inhibition in a concentration-dependent manner. The present study suggests that the d ithiols but not monothiols effectively protect metal-inhibited activit y of PKC in rat brain.