Merckx Ellen, Demuyser Thomas, Bentea Eduard, Van Liefferinge Joeri, Albertini Giulia, Deneyer Lauren, Michiels Thomas, Massie Ann
Department of Pharmaceutical Biotechnology and Molecular Biology, Center for Neurosciences (C4N), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences (C4N), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
Neurosci Lett. 2015 Apr 23;593:124-8. doi: 10.1016/j.neulet.2015.03.026. Epub 2015 Mar 18.
Changes in the expression of xCT, the specific subunit of system xc(-) or the cystine/glutamate antiporter, have been associated with several neurological disorders and system xc(-) was recently proposed as a potential target for the development of new treatment strategies for multiple sclerosis (MS). In this study we used Theiler's murine encephalomyelitis virus (TMEV) infection, both in vitro and in vivo, as a model to further evaluate the involvement of system xc(-) in MS. Protein levels of xCT, as well as activity of system xc(-) were unaffected in RAW264.7 macrophages after infection with the demyelinating DA strain of TMEV. Also, protein expression of xCT remained stable in spinal cord and brain of FVB mice 1-2 and 6 weeks after intracranial injection of the DA strain of TMEV. These results demonstrate that TMEV infection of macrophages or FVB mice has no effect on system xc(-) and as such cannot be used as a model to study the involvement of system xc(-) in MS.
系统xc(-)的特异性亚基xCT（即胱氨酸/谷氨酸反向转运体）的表达变化与多种神经系统疾病相关，且最近有人提出系统xc(-)作为多发性硬化症（MS）新治疗策略开发的潜在靶点。在本研究中，我们使用泰累尔氏小鼠脑脊髓炎病毒（TMEV）感染，包括体外和体内感染，作为进一步评估系统xc(-)在MS中作用的模型。用脱髓鞘的TMEV DA株感染后，RAW264.7巨噬细胞中xCT的蛋白水平以及系统xc(-)的活性未受影响。同样，在颅内注射TMEV DA株1 - 2周和6周后，FVB小鼠脊髓和脑中xCT的蛋白表达保持稳定。这些结果表明，巨噬细胞或FVB小鼠的TMEV感染对系统xc(-)没有影响，因此不能用作研究系统xc(-)在MS中作用的模型。
