Formation of dopamine adducts derived from brain polyunsaturated fatty acids: Mechanism for Parkinson's disease.
J Biol Chem. 2008 Oct 15;
Authors: Liu X, Yamada N, Maruyama W, Osawa T
Oxidative stress appears to be directly involved in the pathogenesis of the neurodegeneration of dopaminergic systems in Parkinson's disease (PD). In this study, we formed four dopamine modification adducts derived from docosahexaenoic acid (DHA, C22:6 / -3) and arachidonic acid (AA, C18:4 / -6) which are known as the major polyunsaturated fatty acids in the brain. Upon incubation of dopamine with fatty acid hydroperoxides and an in vivo experiment using rat brain tissue, all four dopamine adducts were detected. Furthermore, hexanoyl dopamine (HED), an arachidonic acid-derived adduct, caused severe cytotoxicity in human dopaminergic neuroblastoma SH-SY5Y cells while the other adducts only slightly affected. The HED-induced cell death was found to include apoptosis, which also seems to be mediated by reactive oxygen species (ROS) generation and mitochondrial abnormality. Additionally, the experiments using monoamine transporter inhibitor and mouse embryonic fibroblast NIH-3T3 cells that lack the monoamine transporter indicate that the HED-induced cytotoxicity might specially occur in the neuronal cells. These data suggest that the formation of the DHA- and AA-derived dopamine adducts in vitro and in vivo, and HED, the AA-derived dopamine modification adduct, which caused selective cytotoxicity of neuronal cells, may indicate a novel mechanism responsible for the pathogenesis in Parkinson's disease.
PMID: 18922792 [PubMed - as supplied by publisher]