Regulation of ecto-5′-nucleotidase (CD73) in cultured cortical astrocytes by different inflammatory factors
Regulation of ecto-5′-nucleotidase (CD73) in cultured cortical astrocytes by different inflammatory factors
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DOI：
10.1016/j.neuint.2012.06.017
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发表时间：
2012-10-01
影响因子：
4.2
通讯作者：
Nedeljkovic, Nadezda
中科院分区：
文献类型：
--
作者：
Brisevac, Dusica;Bjelobaba, Ivana;Nedeljkovic, Nadezda
外5′-核苷酸酶（e-5NT）是一种位于细胞表面的ATP胞外代谢限速酶，催化AMP转化为腺苷的最后一步。由于这种酶将促炎ATP的平衡转变为抗炎腺苷，因此它被认为是炎症的重要调节剂。尽管在几种脑损伤的体内模型中反复报道了e-5NT的上调，但其表达和功能的调节在很大程度上仍然未知。我们研究了几种促炎因子，即细菌内毒素脂多糖（LPS）、肿瘤坏死因子- α (tnf - α)、干扰素- γ (ifn - γ)、谷氨酸（Glu）和过氧化氢（H2O2）对原代培养皮层星形胶质细胞中e-5NT (i)活性、（ii） mRNA表达和（iii）膜蛋白丰度的影响。我们清楚地证明了e-5NT通路的刺激特异性调节。ifn - γ、LPS、Glu和H2O2降低，tnf - α增加e-5NT活性。对e-5NT基因表达和e-5NT膜蛋白水平的分析表明，所测因子对e-5NT的调控水平不同，机制也不同。总之，我们提供的证据表明，e-5NT的活性以刺激特异性的方式受到严格调节。(C) 2012 Elsevier Ltd.版权所有。
Ecto-5'-nucleotidase (e-5NT) is a cell-surface located, rate-limiting enzyme in the extracellular metabolism of ATP, catalyzing the final step of the conversion of AMP to adenosine. Since this enzyme shifts the balance from pro-inflammatory ATP to anti-inflammatory adenosine, it is considered to be an important regulator of inflammation. Although up-regulation of e-5NT was repeatedly reported in several in vivo models of brain injury, the regulation of its expression and function remains largely unknown. We have studied effects of several pro-inflammatory factors, namely, bacterial endotoxin lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), glutamate (Glu) and hydrogen peroxide (H2O2) on e-5NT (i) activity, (ii) mRNA expression and (iii) membrane protein abundance in primary cultured cortical astrocytes. We are clearly able to demonstrate a stimulus-specific regulation of the e-5NT pathway. IFN-gamma, LPS, Glu and H2O2 decrease, while TNF-alpha increases e-5NT activity. The analysis of e-5NT gene expression and e-5NT membrane protein levels revealed that tested factors regulate e-5NT at different levels and by employing different mechanisms. In summary, we provide evidence that e-5NT activity is tightly regulated in a stimulus-specific manner. (C) 2012 Elsevier Ltd. All rights reserved.