Role of oxidative stress in the manganese and 1-methyl-4-(2'-ethylphenyl)-1,2,3,6-tetrahydropyridine-induced apoptosis in PC12 cells
Role of oxidative stress in the manganese and 1-methyl-4-(2'-ethylphenyl)-1,2,3,6-tetrahydropyridine-induced apoptosis in PC12 cells
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DOI：
10.1016/s0197-0186(96)00146-5
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发表时间：
1997-08-01
影响因子：
4.2
通讯作者：
Miele, E
中科院分区：
文献类型：
--
作者：
Desole, MS;Sciola, L;Miele, E
氧化应激被认为在包括神经元在内的几种细胞系统的凋亡中起关键作用。氧化应激也被认为是神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)-和锰（Mn）诱导的神经元死亡的机制。我们最近发现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），被MAO-A代谢成1-甲基-4-（2’-乙基苯基）-吡啶离子，诱导PC12细胞凋亡。在本研究中，我们评估了去戊烯基和抗氧化药物n-乙酰半胱氨酸（NAC）和抗坏血酸（AA）对Mn-和2' et - mptp诱导的PC12细胞凋亡的影响。采用末端脱氧核苷酸转移酶介导的2'-脱氧尿苷-5'-三磷酸缺口端标记（TUNEL）技术、流式细胞术和荧光显微镜检测细胞凋亡。采用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四唑（MTT）法测定细胞活力。抗氧化剂NAC和AA可抑制mn诱导的细胞凋亡和细胞活力下降。去丙烯醇未能抑制上述Mn效应。NAC、AA和去戊烯醇均不能抑制2' et - mptp诱导的细胞凋亡和细胞活力下降。这些结果证实细胞凋亡可能是MPTP和mn诱导的帕金森病细胞死亡的重要机制。然而，至少在体外，氧化应激机制可能只在锰诱导的细胞凋亡中被认识到。1997爱思唯尔科学有限公司
Oxidative stress is thought to play a key role in the apoptotic death of several cellular systems, including neurons. Oxidative stress is proposed also as a mechanism of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- and manganese (Mn)-induced neuronal death. We have recently shown 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, induce apoptosis in PC12 cells. In the present study, we evaluated the effects of deprenyl and the antioxidant drugs N-acetylcysteine (NAC) and ascorbic acid (AA) on Mn- and 2'Et-MPTP-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. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Mn-induced apoptosis and decrease in cell viability was inhibited by the antioxidants NAC and AA. Deprenyl failed to inhibit the above Mn effects. Neither NAC, AA nor deprenyl were able to inhibit both 2'Et-MPTP-induced apoptosis and decrease in cell viability. These results confirm that apoptosis may be an important mechanism of cell death in MPTP- and Mn-induced parkinsonism. However, an oxidative stress mechanism may be recognized, at least in vitro, only in the Mn-induced apoptosis. (C) 1997 Elsevier Science Ltd.