神經(jīng)病靶酯酶（neuropathy target esterase，NTE）是在研究有機磷化合物（OP）引發(fā)人和敏感動物出現(xiàn)有機磷誘發(fā)的遲發(fā)性退行性病變（OP-induced delayed neuropathy,，OPIDN）時發(fā)現(xiàn)的,。OPIDN發(fā)生時，由于脊髓和周圍神經(jīng)的長軸突退變而導致下肢麻痹甚至癱瘓,。有研究顯示,，NTE的抑制和老化被認為是OPIDN發(fā)生的前提條件。NTE是存在于內(nèi)質(zhì)網(wǎng)上的具有磷脂酶B催化活性的膜蛋白,，在胚胎發(fā)育和神經(jīng)發(fā)育中扮演著重要的角色,。NTE蛋白的N端存在3個可與cAMP結(jié)合的調(diào)節(jié)域，意味著NTE可能受cAMP的調(diào)節(jié),。
中國科學院動物研究所伍一軍研究組的科研人員證實,，雖然cAMP不能改變外源性NTE在細胞中的活性和蛋白表達水平；但增加cAMP可以增加細胞中內(nèi)源性NTE酶活性,，同時,，NTE蛋白表達水平及mRNA水平也相應增加；相反,，如果降低cAMP水平,，可導致細胞內(nèi)源性NTE酶活性以及NTE蛋白表達水平與mRNA水平的降低。
然而,，用蛋白合成抑制劑環(huán)幾亞酰胺（cycloheximide）抑制NTE蛋白合成以后,，無論cAMP增加或降低對細胞內(nèi)NTE活性都沒有影響；抑制細胞內(nèi)PKA活性后細胞內(nèi)NTE酶活性,、NTE蛋白及mRNA的表達明顯降低,；在PKA活性被抑制后，再增加細胞內(nèi)cAMP的含量則檢測不出細胞內(nèi)NTE酯酶活性,、NTE蛋白及mRNA表達的增加,；此外，細胞內(nèi)cAMP增加可以促進甘油磷酸膽堿（GPC）含量的增加,，而cAMP含量的降低和PKA活性抑制可以降低細胞內(nèi)GPC的含量,；同時還發(fā)現(xiàn)，無論cAMP含量增加或降低還是PKA活性增加或降低都不能改變細胞內(nèi)卵磷脂（PC）的含量,。這些結(jié)果表明,，cAMP/PKA信號系統(tǒng)可以促進NTE蛋白的表達并增加細胞內(nèi)GPC的含量。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
