R-(-)-Deprenyl (deprenyl, selegiline), a monoamine oxidase B (MAO-B) inhibitor, delays progression of Parkinson's disease. This action could be mediated by inhibition of MAO-B but there may also be unrelated mechanisms. Direct neuroprotective and antiapoptotic actions of deprenyl have previously been observed in vitro. Here we describe an antineurotoxic action of deprenyl which is independent of direct neuronal effects. We employed a previously described assay in which human neuroblastoma SH-SY5Y cells are exposed to cell-free supernatants of stimulated human monocytic THP-1 cells. Deprenyl reduced the secretion of neurotoxic products by such stimulated cells in a concentration-dependent manner, while the MAO inhibitors iproniazid, isocarboxazid, nialamide, tranylcypromine, phenelzine, and clorgyline were without effect. No antineurotoxic action was observed when deprenyl was added directly to SH-SY5Y cells. Messenger RNAs for MAO-A and MAO-B were not detected in THP-1 cells by reverse transcriptase-polymerase chain reaction analysis of total RNA extracts. Such mRNAs were easily detected in extracts of SH-SY5Y cells under comparable conditions. MAO enzymatic activity was also undetectable in THP-1 cell lysates, while it was readily observed in SH-SY5Y cells. It was concluded that the effect of deprenyl on THP-1 cells was not mediated by MAO and that deprenyl itself was not protecting neurons. These data suggest that deprenyl may have utility in neurodegenerative diseases due to its antineurotoxic actions.

译文

R-(-)-异戊二烯基 (Deprenyl,司来吉兰),一种单胺氧化酶B (mao-b) 抑制剂,可延缓帕金森氏病的进展。这种作用可以通过抑制mao-b来介导,但也可能存在不相关的机制。先前已在体外观察到异戊二烯基的直接神经保护和抗凋亡作用。在这里,我们描述了异戊二烯基的抗神经毒性作用,该作用与直接神经元作用无关。我们采用了先前描述的测定,其中人神经母细胞瘤SH-SY5Y细胞暴露于受刺激的人单核THP-1细胞的无细胞上清液。异戊二烯基以浓度依赖性方式减少了此类刺激细胞对神经毒性产物的分泌,而MAO抑制剂异丙嗪,异卡索嗪,烟酰胺,反苯环丙胺,苯乙嗪和氯代林则无效。当将异戊二烯基直接添加到SH-SY5Y细胞中时,没有观察到抗神经毒性作用。通过总RNA提取物的逆转录酶-聚合酶链反应分析,未在THP-1细胞中检测到mao-a和mao-b的信使RNA。在可比较的条件下,在SH-SY5Y细胞的提取物中容易地检测到这种mrna。在THP-1细胞裂解物中也无法检测到MAO酶活性,而在SH-SY5Y细胞中很容易观察到MAO酶活性。结论是,deprenyl对THP-1细胞的作用不是由MAO介导的,并且deprenyl本身不能保护神经元。这些数据表明,由于其抗神经毒性作用,deprenyl可能在神经退行性疾病中有用。

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