THE COMBINATION OF LEAD WITH A PROTEIN-KINASE-C INHIBITOR CAUSES OXIDATIVE STRESS IN HUMAN NEUROBLASTOMA-CELLS

Lead, when combined with a new specific protein kinase C (PKC) inhibit or, Ro 31-7549, increased the production of reactive oxygen species (R OS), decreased cellular glutathione levels, and induced cytotoxicity i n human SH-SY5Y neuroblastoma cells. Inhibition of PKC may modify the activity of calcium channels, and render them permeable to lead. Lead may then enter the cell and mimick calcium in cellular enzymatic respo nses. Thus, state of phosphorylation of PKC target proteins, Ca2+ chan nels and ROS producing enzymes, may be an important factor in lead neu rotoxicity. Activation of both types of proteins would amplify biologi cal effects of lead and subsequent toxicity.