Laboratory for Molecular Neurobiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloska 4, 1000 Ljubljana, Slovenia.
Chem Biol Interact. 2010 Sep 6;187(1-3):96-100. doi: 10.1016/j.cbi.2010.03.034. Epub 2010 Mar 23.
The best established role of acetylcholinesterase (EC 3.1.1.7, AChE) is termination of neurotransmission at cholinergic synapses. However, AChE is also located at sites, where no other cholinergic components are present and there is accumulating evidence for non-cholinergic functions of this protein. In the process of skeletal muscle formation, AChE is expressed already at the stage of mononuclear myoblast, which is long before other cholinergic components can be demonstrated in this tissue. Myoblast proliferation is an essential step in muscle regeneration and is always accompanied by apoptosis. Since there are several reports demonstrating AChE participation in apoptosis one can hypothesize that early AChE expression in myoblasts reflects the development of the apoptotic apparatus in these cells. Here we tested this hypothesis by following the effect of siRNA AChE silencing on apoptotic markers and by determination of AChE level after staurosporine-induced apoptosis in cultured human myoblasts. Decreased apoptosis in siRNA AChE silenced myoblasts and increased AChE expression in staurosporine-treated myoblasts confirmed AChE involvement in apoptosis. The three AChE splice variants were differently affected by staurosporine-induced apoptosis. The hydrophobic (H) variant appeared unaffected, a tendency towards increase of tailed (T) variant was detected, however the highest, 8-fold increase was observed for readthrough (R) variant. In the light of these findings AChE appears to be a potential therapeutic target at muscle injuries including organophosphate myopathy.
乙酰胆碱酯酶（EC 3.1.1.7，AChE）最确定的作用是终止胆碱能突触的神经传递。然而，AChE 也位于没有其他胆碱能成分存在的部位，并且有越来越多的证据表明该蛋白具有非胆碱能功能。在骨骼肌形成过程中，AChE 已经在单核成肌细胞阶段表达，这比在该组织中可以证明其他胆碱能成分早得多。成肌细胞增殖是肌肉再生的一个重要步骤，总是伴随着细胞凋亡。由于有几个报道表明 AChE 参与细胞凋亡，因此可以假设成肌细胞中早期 AChE 的表达反映了这些细胞中凋亡装置的发展。在这里，我们通过观察 siRNA AChE 沉默对凋亡标志物的影响，并通过确定在培养的人成肌细胞中用 staurosporine 诱导凋亡后的 AChE 水平来检验这一假设。在 siRNA AChE 沉默的成肌细胞中凋亡减少，以及在用 staurosporine 处理的成肌细胞中 AChE 表达增加，证实了 AChE 参与凋亡。三种 AChE 剪接变体对 staurosporine 诱导的凋亡有不同的影响。疏水性（H）变体似乎不受影响，检测到长尾（T）变体有增加的趋势，但观察到最高的 8 倍增加是通读（R）变体。鉴于这些发现，AChE 似乎是肌肉损伤包括有机磷中毒性肌病的潜在治疗靶点。
