The effect of Epoxyeicosatrienoic acids on oxidative stress‐induced apoptosis in mesencephalic dopaminergic neuronal cells.

Abstract

Oxidative stress and apoptotic cell death have been implicated in the dopaminergic cell loss that characterizes Parkinson's disease. While factors contributing to apoptotic cell death are not well characterized, oxidative stress is known to activate an array of cell signaling molecules that participate in apoptotic cell death mechanisms. Furthermore, epoxyeicosatrienoic acids (EETs) such as 14,15‐EET have been recognized for their protective effects on the cardiovascular system. In this study, we are investigating the effect of EETs on oxidative stress‐induced cytotoxicity by hydrogen peroxide (H2O2) in the dopaminergic mesencephalon‐derived N27 cell line. N27 cells stimulated with different doses of H202 (0.01 to 5mM for 4h) produce dose‐dependent oxidative stress‐induced apoptotic cell death. N27 cells stimulated with H2O2 increase the oxidation of PTEN and increased the phosphorylation of Akt. However, N27 cells stimulated with a high dose of 14,15‐EET (3μM) did not oxidize PTEN, but showed a decrease in Akt phosphorylation. These data make it essential to understand the role of EETs in protecting dopaminergic neurons from oxidative stress, which may help in understanding deficits seen in Parkinson's disease. Support: NIH/NHLBI PO1 HL59996‐05; RO1 HL33833‐17; RO1 HL092105‐01A1.