A novel role of protein kinase C-δ in cell signaling triggered by glutathione depletion

Current evidence demonstrates that protein kinase C (PKC) belongs to a group of cell-signaling molecules that are sensitive targets for redox modifications and functional alterations that mediate oxidant-induced cellular responses. Our studies have demonstrated that diminished intracellular GSH was associated to inactivation of classic isoforms and increased activity of novel PKCs, and triggered molecular signals important for cell survival. Loss of GSH and oxidative damage are probably an early signaling event in apoptotic death, which is characterized by the activation of PKC-delta. Apoptotic process consequent to GSH depletion was inhibited by rottlerin, a PKC-delta-specific inhibitor, which exerted a negative effect on oxyradical production. Therefore, it may be concluded that PKC-delta activity is related to reactive oxygen species production and is involved in the pathway leading to apoptosis and growth arrest. (C) 2003 Elsevier Inc. All rights reserved.