Involvement of Lipid Peroxidation in the Alteration of Protein Kinase C Signaling

Abstract

Numerous studies have shown that lipid peroxidation is involved in the pathogenesis of various degenerative diseases including atherosclerosis, diabetes, cancer, inflammation, drug-induced toxicity, and neurodegenerative disease. Protein kinase C (PKC), a lipid activated kinase, is a key enzyme for intracellular signaling pathway in physiological conditions. Recently considerable evidence has accumulated to confirm that lipid peroxidation participates in intracellular signal transduction in the pathophysiology of aerobic organisms. Lipid peroxides, such as hydroperoxy fatty acids, oxidized cholesteryl linoleates and 4-hydroxy-2-nonenal, efficiently stimulate PKC in the cells. More importantly, oxidized diacylglycerol strongly stimulates PKC as much as phorbol ester, a strong tumor-promoting PKC activator. This review article describes PKC signaling pathway, the role of lipid peroxides in the intracellular signaling, the significance of lipid peroxidation in pathophysiology, and the cellular defense systems against oxidative stress.