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首页> 外文期刊>Life sciences >Degradation of neuropathy target esterase by the macroautophagic lysosomal pathway.
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Degradation of neuropathy target esterase by the macroautophagic lysosomal pathway.

机译：大自噬溶酶体途径对神经病靶标酯酶的降解作用。

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AIMS: Neuropathy target esterase (NTE) was proposed as the initial target during the process of organophosphate-induced delayed neuropathy (OPIDN) in humans and some sensitive animals. NTE was recently identified as a novel phospholipase B that is anchored to the cytoplasmic side of the endoplasmic reticulum. However, little is known about the degradation of NTE. In this study, we have investigated the role of the macroautophagic-lysosomal pathway in NTE degradation in neuronal and non-neuronal cells. MAIN METHODS: Macroautophagy inhibitors and activators were used to interrupt the lysosomal pathway, and NTE protein level was followed using western blotting analysis. A fluorescent microscopy assay was used to determine the co-localization of NTE and lysosomes. KEY FINDINGS: Western blotting analysis showed that the macroautophagy inhibitors 3-methyladenine and ammonium chloride increased the levels of a heterologously expressed NTE-GFP fusion protein as well as endogenous NTE. Starvation had the opposite effect. The role of macroautophagy in NTE degradation was further supported by the co-localization of exogenous NTE with lysosomes in starved COS7 cells. Furthermore, the contribution of NTE activity and protein domains to the degradation of NTE by macroautophagy was investigated, showing that both the transmembrane and regulatory domains played a role in the degradation of NTE and that the catalytic domain, and thus NTE activity, was not involved. SIGNIFICANCE: Our findings clearly demonstrate, for the first time, that the macroautophagy/lysosome pathway plays a role in controlling NTE quantity, providing a further understanding of the function of NTE.
机译：目的：神经病性目标酯酶（NTE）被提议作为人类和某些敏感动物中有机磷酸酯诱导的迟发性神经病（OPIDN）过程的最初目标。 NTE最近被确定为一种新型磷脂酶B，可锚定在内质网的细胞质侧。然而，关于NTE的降解了解甚少。在这项研究中，我们调查了巨噬细胞溶酶体途径在神经元和非神经元细胞NTE降解中的作用。主要方法：使用巨噬细胞自噬抑制剂和激活剂来中断溶酶体途径，并通过蛋白质印迹分析来追踪NTE蛋白水平。使用荧光显微镜测定法确定NTE和溶酶体的共定位。主要发现：Western印迹分析表明，巨噬细胞自噬抑制剂3-甲基腺嘌呤和氯化铵增加了异源表达的NTE-GFP融合蛋白以及内源性NTE的水平。饥饿产生相反的效果。在饥饿的COS7细胞中，外源性NTE与溶酶体的共定位进一步支持了巨噬细胞在NTE降解中的作用。此外，研究了NTE活性和蛋白质结构域对通过巨噬自噬降解NTE的贡献，表明跨膜和调节结构域均在NTE降解中起作用，并且催化结构域和NTE活性均不参与。意义：我们的发现首次清楚地表明，巨噬细胞自噬/溶酶体途径在控制NTE数量方面发挥了作用，从而进一步了解了NTE的功能。

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