Possible role of interleukin-6 in PC12 cell death induced by MPP+ and tetrahydroisoquinoline.
Possible role of interleukin-6 in PC12 cell death induced by MPP+ and tetrahydroisoquinoline.
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DOI：
10.1254/jphs.93.471
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发表时间：
2003
影响因子：
3.5
通讯作者：
Naoko Shimma;N. Akiyama;M. Umezawa;Y. Okuma;Y. Nomura;T. Saito;S. Horie;T. Murayama
中科院分区：
文献类型：
--
作者：
Naoko Shimma;N. Akiyama;M. Umezawa;Y. Okuma;Y. Nomura;T. Saito;S. Horie;T. Murayama
白细胞介素（IL）-6已被证明可以保护神经元细胞免受各种刺激剂诱导的细胞死亡。尽管包括PC 12细胞在内的神经元细胞被证明可以产生IL-6，但人们对多巴胺能神经毒素1，2，3，4-四氢异喹啉（TIQ）和1-甲基-4-苯基吡啶离子（MPP（+））对PC 12细胞中IL-6表达的影响知之甚少。在本研究中，我们研究了IL-6在TIQ和MPP（+）诱导的PC 12细胞死亡中的作用。用3.2 mM TIQ处理24 h后，在添加后72 h显著引起延迟的细胞死亡（乳酸脱氢酶（LDH）泄漏和核DNA片段化）。加入0.4mMMPP（+）后24 h引起LDH漏出和核DNA断裂。半胱天冬酶抑制剂z-Val-Ala-Asp（OMe）-fluoromethylketone可抑制MPP（+）诱导的细胞死亡。神经生长因子和10%血清可抑制TIQ或MPP（+）诱导的细胞死亡，抗IL-6抗体可显著增强TIQ或MPP（+）诱导的细胞死亡。两种神经毒素均降低PC 12细胞中IL-6 mRNA水平，而不改变其他测试的mRNA水平（IL-1 α、β-肌动蛋白等）。这些发现表明多巴胺能神经毒素至少部分通过改变IL-6表达引起PC 12细胞的细胞死亡。
Interleukin (IL)-6 has been shown to protect neuronal cells from cell death induced by various stimulants. Although neuronal cells including PC12 cells were shown to produce IL-6, little is known about the effects of dopaminergic neurotoxins, 1,2,3,4-tetrahydroisoquinoline (TIQ) and 1-methyl-4-phenylpyridinium ion (MPP(+)), on IL-6 expression in PC12 cells. In the present study, we investigated the role of IL-6 in the TIQ- and MPP(+)-induced cell death in PC12 cells. Treatment with 3.2 mM TIQ for 24 h caused a delayed cell death (lactate dehydrogenase (LDH) leakage and nuclear DNA fragmentation) markedly 72 h after the addition. Addition of 0.4 mM MPP(+) caused LDH leakage and nuclear DNA fragmentation 24 h after the addition. The cell death induced by MPP(+) was inhibited by an inhibitor of caspases, z-Val-Ala-Asp(OMe)-fluoromethylketone. The cell death induced by TIQ or MPP(+) was inhibited by nerve growth factor and 10% serum and significantly enhanced by the treatment with anti-IL-6 antibody. Both neurotoxins decreased the IL-6 mRNA level in PC12 cells without changing the other tested mRNA levels (IL-1 alpha, beta-actin, etc.). These findings suggest that dopaminergic neurotoxins cause cell death in PC12 cells at least partially by changing IL-6 expression.