神经病靶酯酶（neuropathy target esterase，NTE）是在研究有机磷化合物（OP）引发人和敏感动物出现有机磷诱发的迟发性退行性病变（OP-induced delayed neuropathy，OPIDN）时发现的。OPIDN发生时，由于脊髓和周围神经的长轴突退变而导致下肢麻痹甚至瘫痪。有研究显示，NTE的抑制和老化被认为是OPIDN发生的前提条件。NTE是存在于内质网上的具有磷脂酶B催化活性的膜蛋白，在胚胎发育和神经发育中扮演着重要的角色。NTE蛋白的N端存在3个可与cAMP结合的调节域，意味着NTE可能受cAMP的调节。
中国科学院动物研究所伍一军研究组的科研人员证实，虽然cAMP不能改变外源性NTE在细胞中的活性和蛋白表达水平；但增加cAMP可以增加细胞中内源性NTE酶活性，同时，NTE蛋白表达水平及mRNA水平也相应增加；相反，如果降低cAMP水平，可导致细胞内源性NTE酶活性以及NTE蛋白表达水平与mRNA水平的降低。
然而，用蛋白合成抑制剂环几亚酰胺（cycloheximide）抑制NTE蛋白合成以后，无论cAMP增加或降低对细胞内NTE活性都没有影响；抑制细胞内PKA活性后细胞内NTE酶活性、NTE蛋白及mRNA的表达明显降低；在PKA活性被抑制后，再增加细胞内cAMP的含量则检测不出细胞内NTE酯酶活性、NTE蛋白及mRNA表达的增加；此外，细胞内cAMP增加可以促进甘油磷酸胆碱（GPC）含量的增加，而cAMP含量的降低和PKA活性抑制可以降低细胞内GPC的含量；同时还发现，无论cAMP含量增加或降低还是PKA活性增加或降低都不能改变细胞内卵磷脂（PC）的含量。这些结果表明，cAMP/PKA信号系统可以促进NTE蛋白的表达并增加细胞内GPC的含量。
生物谷推荐原文出处：
Pharmacological Research doi:10.1016/j.phrs.2010.03.006
Regulation of neuropathy target esterase by the cAMP/protein kinase A signal
Jia-Xiang Chena, b, c, Ding-Xin Longa, b, Wei-Yuan Houa, b, Wei Lia and Yi-Jun Wua, ,
a Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichenxi Road, Chaoyang District, Beijing 100101, PR China
b Graduate University of Chinese Academy of Sciences, Beijing 100039, PR China
c Medical School of Nanchang University, Nanchang 330006, PR China
As a phospholipase B, neuropathy target esterase (NTE) is responsible for the conversion of phosphatidylcholine (PC) to glycerophosphocholine (GPC). We examined the role of cAMP in the regulation of NTE in mammalian cells. Endogenous NTE activity was increased by cAMP-elevating chemicals, including dibutyryl cAMP, forskolin and forskolin plus 1-isobutyl-3-methylxanthine (IBMX), but decreased by the adenyl cyclase inhibitor SQ22536 which can reduce intracellular cAMP levels. Exogenous GFP-tagged NTE activity was not affected by changes in intracellular cAMP. NTE protein levels were up-regulated by the cAMP-elevating reagents and down-regulated by the inhibitor. The effect of the adenyl cyclase activator forskolin on NTE protein and mRNA levels was blocked by pretreatment with the protein kinase A (PKA) activity inhibitor H89. In addition, we found that changes in GPC, but not PC, levels were correlated with cAMP induced changes in NTE activity. These results are the first evidence that cAMP/PKA signals regulate NTE expression and GPC content in mammalian cells.
