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1,2,3,4-四氢-β-咔啉与香烟烟雾相互作用的研究:帕金森病神经保护的潜在机制

Studies on the interaction between 1,2,3,4-tetrahydro-beta-carboline and cigarette smoke: a potential mechanism of neuroprotection for Parkinson's disease.

作者信息

Soto-Otero R, Méndez-Alvarez E, Riguera-Vega R, Quiñoá-Cabana E, Sánchez-Sellero I, López-Rivadulla Lamas M

机构信息

Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universidad de Santiago de Compostela, Spain.

出版信息

Brain Res. 1998 Aug 17;802(1-2):155-62. doi: 10.1016/s0006-8993(98)00538-1.

DOI:10.1016/s0006-8993(98)00538-1
PMID:9748553
Abstract

1,2,3,4-Tetrahydro-beta-carboline (TH beta C) is an endogenous or environmental neurotoxic factor putatively involved in the development of Parkinson's disease (PD). As part of our efforts to characterize the mechanism of the reported protection of smoking against PD, we have examined the interaction between TH beta C and cigarette smoke. We found that TH beta C reacts in vitro and under physiological conditions with some components of cigarette smoke to form N2-(cyanomethyl)-TH beta C (CM-TH beta C), N2-(gamma-cyanoethyl)-TH beta C (CE-TH beta C), N2-(1'-cyanopropyl)-TH beta C (CP-TH beta C), N2-(1'-cyanobutyl)-TH beta C (CB-TH beta C) and N2-formyl-TH beta C (F-TH beta C). Significant differences in the recovery of some of these TH beta C-derivatives were obtained for Burley and Bright tobacco. Several of the reported compounds showed reversible and competitive MAO-A inhibitory properties. The detection of some of these compounds in rat brain after chronic administration of TH beta C and a solution of cigarette smoke proved that the reported interactions also occur in vivo. These results are discussed as a potential mechanism of neuroprotection in the development of PD.

摘要

1,2,3,4-四氢-β-咔啉(THβC)是一种内源性或环境性神经毒性因子,被认为与帕金森病(PD)的发生发展有关。作为我们对已报道的吸烟对PD具有保护作用机制进行研究的一部分,我们研究了THβC与香烟烟雾之间的相互作用。我们发现,THβC在体外和生理条件下与香烟烟雾的某些成分发生反应,形成N2-(氰甲基)-THβC(CM-THβC)、N2-(γ-氰乙基)-THβC(CE-THβC)、N2-(1'-氰丙基)-THβC(CP-THβC)、N2-(1'-氰丁基)-THβC(CB-THβC)和N2-甲酰基-THβC(F-THβC)。白肋烟和烤烟在这些THβC衍生物的回收率上存在显著差异。所报道的几种化合物表现出可逆和竞争性的单胺氧化酶-A抑制特性。在长期给予THβC和香烟烟雾溶液后,在大鼠脑中检测到其中一些化合物,证明所报道的相互作用也发生在体内。这些结果作为PD发生发展中神经保护的潜在机制进行了讨论。

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