Ma Zhizhong, Wei Xing, Fontanilla Christine, Noelker Carmen, Dodel Richard, Hampel Harald, Du Yansheng
Department of Neurology, Indiana University School of Medicine, 975 West Walnut Street, Rm 457, Indianapolis, IN 46202, USA.
Life Sci. 2006 Aug 22;79(13):1307-11. doi: 10.1016/j.lfs.2006.03.050. Epub 2006 Apr 26.
Neurotoxicity induced by 6-hydroxydopamine (6-OHDA) is believed to be due, in part, to the production of reactive oxygen species (ROS). Antioxidants protect neurons against 6-OHDA-induced neurotoxicity by inhibiting free radical generation. In this study, we investigated whether or not caffeic acid phenethyl ester (CAPE) could protect neurons against 6-OHDA-induced neurotoxicity in cultured rat rostral mesencephalic neurons (RMN) and cerebellar granule neurons (CGN). We now report that exposure of RMN and CGN to 6-OHDA (40 microM for RMN and 70 microM for CGN) resulted in significant increases in free radical production and death of both neuron types. Pretreatment with CAPE (10 microM) for 2 h prevented both 6-OHDA-induced free radical generation and neurotoxicity. Furthermore, CAPE also attenuated H(2)O(2)-induced neurotoxicity. Our results strongly suggest that CAPE blocks 6-OHDA-induced neuronal death possibly by inhibiting 6-OHDA-induced free radical generation and blocking free radical-induced neurotoxicity in neurons. Both the antioxidative and neuroprotective effects of CAPE may be beneficial in the therapy for Parkinson's disease and other neurodegenerative diseases.
6-羟基多巴胺（6-OHDA）诱导的神经毒性被认为部分归因于活性氧（ROS）的产生。抗氧化剂通过抑制自由基生成来保护神经元免受6-OHDA诱导的神经毒性。在本研究中，我们调查了咖啡酸苯乙酯（CAPE）是否能保护培养的大鼠中脑嘴侧神经元（RMN）和小脑颗粒神经元（CGN）免受6-OHDA诱导的神经毒性。我们现在报告，RMN和CGN暴露于6-OHDA（RMN为40 microM，CGN为70 microM）导致两种神经元类型的自由基产生显著增加和死亡。用CAPE（10 microM）预处理2小时可防止6-OHDA诱导的自由基生成和神经毒性。此外，CAPE还减弱了H2O2诱导的神经毒性。我们的结果强烈表明，CAPE可能通过抑制6-OHDA诱导的自由基生成并阻断自由基诱导的神经元神经毒性来阻止6-OHDA诱导的神经元死亡。CAPE的抗氧化和神经保护作用可能对帕金森病和其他神经退行性疾病的治疗有益。
