Desole M S, Sciola L, Delogu M R, Sircana S, Migheli R
Institute of Pharmacology, University of Sassari, Italy.
Neurosci Lett. 1996 May 17;209(3):193-6. doi: 10.1016/0304-3940(96)12645-8.
Oxidative stress is thought to play a key role both in the neurotoxin MPTP- and manganese (Mn)-induced neurotoxicity and in apoptotic cell death. In the present study, we report that Mn and the MPTP analogue 1-methyl-4-(2'-ethylphenyl)-1,2,3,6-tetrahydropyridine (2'Et-MPTP), which is metabolized by MAO-A to 1-methyl-4-(2'-ethylphenyl)-pyridinium ion (at concentrations of 0.5 and 1.0 mM), induced apoptosis in PC12 cells. Apoptosis was tested by terminal deoxynucleotidyl transferase-mediated 2'-deoxy-uridine-5'-triphosphate nick end labelling (TUNEL) technique, flow cytometry and fluorescence microscopy. Both Mn and 2'Et-MPTP induced also a time-dependent decrease in cell viability, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Only Mn-induced apoptosis and decrease in cell viability were inhibited by the antioxidant ascorbic acid. We conclude that apoptosis may be an important mechanism of cell death in MPTP- and Mn-induced parkinsonism. However, an oxidative stress mechanism may be recognized only in the Mn-induced apoptosis.
氧化应激被认为在神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）和锰（Mn）诱导的神经毒性以及凋亡性细胞死亡中均起关键作用。在本研究中，我们报告称，Mn和MPTP类似物1-甲基-4-（2'-乙基苯基）-1,2,3,6-四氢吡啶（2'Et-MPTP，其经单胺氧化酶A（MAO-A）代谢为1-甲基-4-（2'-乙基苯基）-吡啶离子，浓度为0.5和1.0 mM）可诱导PC12细胞凋亡。通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）技术、流式细胞术和荧光显微镜检测凋亡情况。通过3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐（MTT）检测法测定，Mn和2'Et-MPTP均还会导致细胞活力随时间下降。只有Mn诱导的凋亡和细胞活力下降受到抗氧化剂抗坏血酸的抑制。我们得出结论，凋亡可能是MPTP和Mn诱导的帕金森病中细胞死亡的重要机制。然而，氧化应激机制可能仅在Mn诱导的凋亡中存在。
