Effect of lipid peroxidation conditions on calcium-dependent activity of phosphodiesterase 3′,5′-cAMP in the rat brain

Abstract

3',5'-cAMP plays an important role as a second messenger molecule controlling multiple cellular processes in the brain. Its levels are decreased by phosphodiesterases (PDEs), responsible for hydrolysis of intracellular cAMP. A part of the PDE activity is dependent on the effect of calcium, mediated by its binding to calmodulin. During oxidative stress, precisely these changes in calcium concentration are responsible for cell damage. We have examined the effects of oxidative stress conditions on the activity of PDE in rat brain homogenates. We found a different influence of activated lipid peroxidation conditions (Fe 2+ with ascorbate and increased temperature) on the calcium-dependent and calciumindependent PDE activity. The inhibition of Ca 2+ -dependent PDE was observed, while Ca 2+ -independent PDE was not influenced. We assume that it might be the impact of lipid peroxidation products or any mechanism activated by the higher temperature on the interaction of the Ca 2+ -dependent isoform of PDE with the complex calcium-calmodulin. Another explanation might be that the formation of the functioning calcium-calmodulin complex is impossible in these conditions.