Enhancement of dopaminergic neurotoxicity by the mercapturate of dopamine: relevance to Parkinson's disease.

摘要: The mechanisms that underlie dopaminergic neurodegeneration in Parkinson's disease (PD) are not known but have been proposed to involve oxidation of dopamine and related catechols. In other organ systems, cytotoxicity from catechol is profoundly influenced by mercapturate metabolism. Here we tested the hypothesis thioethers produced mercapturic acid pathway may act as neurotoxins. A rat mesencephalic/neuroblastoma hybrid (MES) cell line was exposed dopamine, 3,4-dihydroxyphenylacetic (DOPAC), or eight different for up 24 h, extent apoptosis quantified a microculture kinetic assay. Apoptosis also confirmed morphologically with Giemsa-stained cultures demonstration internucleosomal DNA fragmentation. results showed at 5-50 microM concentration-dependent increases percentage apoptotic MES cells. At 25 50 maximal proportions cells were detected approximately 19 (20.7 +/- 2.0%) 14 h (30.3 3.5%), respectively. None (up 5 microM) alone induced significant However, when incubated (25 (5 mimic pathological conditions, 5-S-N-acetylcysteinyldopamine, 5-S-homocysteinyldopamine, 5-S-homocysteinyl-DOPAC significantly increased compared alone. These suggest metabolism endogenous catechols yield products facilitate neurodegeneration.