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首页> 外文期刊>Cell discovery. >A novel role for synaptic acetylcholinesterase as an apoptotic deoxyribonuclease
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A novel role for synaptic acetylcholinesterase as an apoptotic deoxyribonuclease

机译：突触乙酰胆碱酯酶作为凋亡脱氧核糖核酸酶的新作用

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In addition to terminating neurotransmission by hydrolyzing acetylcholine, synaptic acetylcholinesterase (AChES) has been found to have a pro-apoptotic role. However, the underlying mechanism has rarely been investigated. Here, we report a nuclear translocation-dependent role for AChES as an apoptotic deoxyribonuclease (DNase). AChES polypeptide binds to and cleaves naked DNA at physiological pH in a Ca2+–Mg2+-dependent manner. It also cleaves chromosomal DNA both in pre-fixed and in apoptotic cells. In the presence of a pan-caspase inhibitor, the cleavage still occurred after nuclear translocation of AChES, implying that AChES-DNase acts in a CAD - and EndoG - independent manner. AChE gene knockout impairs apoptotic DNA cleavage; this impairment is rescued by overexpression of the wild-type but not (aa 32–138)-deleted AChES. Furthermore, in comparison with the nuclear-localized wild-type AChES, (aa 32–138)-deleted AChES loses the capacity to initiate apoptosis. These observations confirm that AChES mediates apoptosis via its DNase activity.
机译：除了通过水解乙酰胆碱终止神经传递外，还发现突触乙酰胆碱酯酶（AChE S ）具有促凋亡作用。但是，很少研究其潜在机制。在这里，我们报道AChE S 作为细胞凋亡的脱氧核糖核酸酶（DNase）的核易位依赖性作用。在生理pH下，AChE S 多肽以Ca 2 + –Mg 2 + 依赖性方式结合并切割裸DNA。它还可以在固定细胞和凋亡细胞中裂解染色体DNA。在泛半胱天冬酶抑制剂的存在下，切割仍然发生在AChE S 的核易位后，这表明AChE S -DNase在CAD和EndoG中独立起作用方式。 AChE基因敲除损害凋亡的DNA裂解;这种损伤可以通过野生型的过表达来挽救，但不能缺失（aa 32–138）缺失的AChE S 。此外，与核定位的野生型AChE S 相比，（aa 32–138）缺失的AChE S 丧失了启动凋亡的能力。这些观察结果证实AChE S 通过其DNase活性介导细胞凋亡。

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