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低密度脂蛋白和高密度脂蛋白影响人星形细胞瘤细胞中的一氧化氮代谢。

LDL and HDL affect nitric oxide metabolism in human astrocytoma cells.

作者信息

Nanetti L, Vignini A, Moroni C, Pessina G P, Mazzanti L

机构信息

Institute of Biochemistry, School of Medicine, Polytechnical Marche University, Via P. Ranieri 65, Ancona 6013, Italy.

出版信息

Brain Res. 2004 Sep 10;1020(1-2):173-7. doi: 10.1016/j.brainres.2004.06.026.

DOI:10.1016/j.brainres.2004.06.026
PMID:15312800
Abstract

Astrocytes provide structural, trophic and metabolic support to neurons and modulate synaptic activity. Under physiological conditions, neuronal-derived nitric oxide (NO) plays an important role in the modulation of a variety of central nervous system (CNS) functions. NO, although short lived, can travel sufficient distances to be able to act as an intercellular messenger in the brain. Its targets include adjacent neurons and astrocytes. The aim of the present study was performed in order to investigate the effects produced by incubation of lipoproteins, at different times, with human astrocytoma cells and thus measuring NO and its metabolite production. NO and peroxynitrite production, iNOS and nNOS expression by Western immunoblot were evaluated. The LDL and HDL-treated cells showed an increased production of NO, more evident after 12 h, compared to basal levels; concerning peroxynitrite production, LDL and HDL-treated cells showed a higher fluorescence, more evident at 3 h. nNOS and iNOS protein levels were significantly higher in the cells incubated with control LDL and HDL. The present work supports the hypothesis that lipoproteins can induce the formation of reactive astrocytes, inducing iNOS as reported by other authors, giving experimental support to a role played by LDL and HDL inducing a reactive response.

摘要

星形胶质细胞为神经元提供结构、营养和代谢支持,并调节突触活动。在生理条件下,神经元衍生的一氧化氮(NO)在多种中枢神经系统(CNS)功能的调节中起重要作用。NO虽然寿命短暂,但能够传播足够的距离,从而能够在大脑中充当细胞间信使。其作用靶点包括相邻的神经元和星形胶质细胞。本研究的目的是研究脂蛋白在不同时间与人星形细胞瘤细胞孵育所产生的影响,从而测量NO及其代谢产物的产生。通过Western免疫印迹评估NO和过氧亚硝酸盐的产生、诱导型一氧化氮合酶(iNOS)和神经元型一氧化氮合酶(nNOS)的表达。与基础水平相比,经低密度脂蛋白(LDL)和高密度脂蛋白(HDL)处理的细胞显示出NO产生增加,在12小时后更明显;关于过氧亚硝酸盐的产生,经LDL和HDL处理的细胞显示出更高的荧光,在3小时时更明显。在用对照LDL和HDL孵育的细胞中,nNOS和iNOS蛋白水平显著更高。本研究支持以下假设:脂蛋白可诱导反应性星形胶质细胞的形成,如其他作者所报道的那样诱导iNOS,为LDL和HDL诱导反应性应答所起的作用提供了实验支持。

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引用本文的文献

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Neuromolecular Med. 2008;10(1):17-23. doi: 10.1007/s12017-007-8012-z. Epub 2007 Sep 15.
2
Tissue-type plasminogen activator and the low-density lipoprotein receptor-related protein mediate cerebral ischemia-induced nuclear factor-kappaB pathway activation.组织型纤溶酶原激活剂和低密度脂蛋白受体相关蛋白介导脑缺血诱导的核因子-κB通路激活。
Am J Pathol. 2007 Oct;171(4):1281-90. doi: 10.2353/ajpath.2007.070472. Epub 2007 Aug 23.
3
Signals for the induction of nitric oxide synthase in astrocytes.
星形胶质细胞中一氧化氮合酶诱导的信号
Neurochem Int. 2006 Jul;49(2):154-63. doi: 10.1016/j.neuint.2006.04.007. Epub 2006 Jun 5.