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Assessment of salsolinol N-methyltransferase activity in rat peripheral lymphocytes by liquid chromatography-electrospray time-of-flight mass spectrometry

Zhang, Yongqian, Wang, Lin, Mu, Xiaoling, Duan, Jinyan, Zhu, Yong, Qing, Hong, Li, Yujuan, Xiao, Shengyuan, Deng, Yulin
Analytical and bioanalytical chemistry 2011 v.399 no.10 pp. 3541-3545
Parkinson disease, lymphocytes, mass spectrometry, models, neurons, neurotoxins, pathogenesis, quantitative analysis, rats
Salsolinol N-methyltranseferase (SNMT), which may play a crucial role in the pathogenesis of Parkinson's diseases (PD), is a key enzyme to metabolize salsolinol into N-methylsalsolinol that is a neurotoxin specific to dopaminergic neurons. A sensitive method for the quantitative determination of SNMT activity in rat peripheral lymphocytes was developed and validated using liquid chromatography-electrospray with time-of-flight mass spectrometry (LC-ESI-TOF). The calibration curve was linear over the range of 7.40-368.80 nM, with 7.40 nM of the lower limit of quantification. The inter-day and intra-day precisions and accuracy for all samples were acceptable. The validated method was successfully applied for the determination of SNMT activity in both the substantia nigra (SN) and peripheral lymphocytes of a unilateral 6-hydroxydopamine-lesion model of Parkinson's disease in rats. The SNMT activity in the peripheral lymphocytes treated with the 6-hydroxydopamine was significantly increased compared with the control and sham-operated groups, which was coincident with the alteration of SNMT activity in the SN. Our results might indicate that SNMT activity may become a potential clinical marker for PD.