The combination of lead with a protein kinase C inhibitor causes oxidative stress in human neuroblastoma cells

Abstract

Lead, when combined with a new specific protein kinase C (PKC) inhibitor, Ro 31–7549, increased the production of reactive oxygen species (ROS), decreased cellular glutathione levels, and induced cytotoxicity in 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 responses. Thus, state of phosphorylation of PKC target proteins, Ca2+ channels and ROS producing enzymes, may be an important factor in lead neurotoxicity. Activation of both types of proteins would amplify biological effects of lead and subsequent toxicity.