神经末梢中乙酰辅酶A区室化变化对大脑胆碱能传递障碍的潜在意义。

Putative significance of shifts in acetyl-CoA compartmentalization in nerve terminals for disturbances of cholinergic transmission in brain.

作者信息

Szutowicz A, Tomaszewicz M, Bielarczyk H, Jankowska A

机构信息

Department of Clinical Biochemistry, Medical University of Gdańsk, Gdańsk, Poland.

出版信息

Dev Neurosci. 1998;20(4-5):485-92. doi: 10.1159/000017347.

DOI:10.1159/000017347

PMID:9778588

Abstract

Acetylcholine and acetyl-CoA metabolism in nerve terminals isolated from rat brain were found to be affected by several neurotoxic and neuroprotective agents, such as aluminium, nitric oxide, beta-hydroxybutyrate, verapamil and thiamine deficiency. The changes evoked by these factors in Ca2+-dependent acetylcholine release were highly significantly correlated (r = 0.98) with changes in concentration of synaptoplasmic acetyl-CoA. On the other hand, in the same experimental conditions, no correlation was found between rates of pyruvate oxidation, intramitochondrial acetyl-CoA levels and different pools of releasable acetylcholine. These data indicate that disturbances in the availability of acetyl-CoA in the cytoplasm of nerve terminals may be a key factor in the pathogenesis of several cholinergic encephalopathies.

摘要

从大鼠脑中分离出的神经末梢中，乙酰胆碱和乙酰辅酶A的代谢被发现受到多种神经毒性和神经保护剂的影响，如铝、一氧化氮、β-羟基丁酸、维拉帕米和硫胺缺乏。这些因素引起的Ca2+依赖性乙酰胆碱释放变化与突触质乙酰辅酶A浓度变化高度显著相关（r = 0.98）。另一方面，在相同实验条件下，丙酮酸氧化速率、线粒体内乙酰辅酶A水平与不同可释放乙酰胆碱池之间未发现相关性。这些数据表明，神经末梢细胞质中乙酰辅酶A可用性的紊乱可能是几种胆碱能脑病发病机制中的关键因素。