Diagnostic copper imaging of Menkes disease by synchrotron radiation-generated X-ray fluorescence analysis.
Diagnostic copper imaging of Menkes disease by synchrotron radiation-generated X-ray fluorescence analysis.
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DOI：
10.1038/srep33247
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发表时间：
2016-09-15
影响因子：
4.6
通讯作者：
Kimura S
中科院分区：
文献类型：
--
作者：
Kinebuchi M;Matsuura A;Kiyono T;Nomura Y;Kimura S
铜（Cu）是人体正常发育和功能，特别是中枢神经系统（CNS）不可缺少的金属。然而，其氧化还原活性需要精确的铜转运系统。ATP7A是一种主要的Cu2+转运atp酶，是铜跨质膜外排和合成铜原酶所必需的。门克斯病（MD）是由ATP7A基因突变引起的疾病。临床上，MD为缺铜综合征，确诊后立即用组氨酸铜注射治疗。但大多数人的结果仍然很差。为了估计标准治疗，通过同步辐射产生的x射线荧光技术（SR-XRF）分析治疗的经典MD患者中的Cu分布，该技术可以识别和量化单个原子，分辨率达到亚细胞水平，检测范围广。SR-XRF分析新发现Cu存在于脊髓实质中，并通过静脉和淋巴系统流出。通过系统分析，在肾近端小管细胞、肠粘膜上皮细胞以及淋巴和静脉系统中检测到过量的Cu。目前的研究表明，标准疗法为患者组织提供了几乎足够的铜。但是给定的铜通过组织进入静脉和淋巴系统，或者在负责吸收铜的细胞中积累。
Copper (Cu) is an indispensable metal for normal development and function of humans, especially in central nervous system (CNS). However, its redox activity requires accurate Cu transport system. ATP7A, a main Cu2+ transporting-ATPase, is necessary to efflux Cu across the plasma membrane and synthesize cuproenzymes. Menkes disease (MD) is caused by mutations in ATP7A gene. Clinically, MD is Cu deficiency syndrome and is treated with Cu-histidine injections soon after definite diagnosis. But outcome of the most remains poor. To estimate the standard therapy, Cu distribution in the treated classic MD patients is analyzed by synchrotron-generated X-ray fluorescence technique (SR-XRF), which identifies and quantifies an individual atom up to at subcellular level of resolution with wide detection area. SR-XRF analysis newly reveals that Cu exists in spinal cord parenchyma and flows out via venous and lymph systems. By systemic analysis, excess Cu is detected in the proximal tubular cells of the kidney, the mucosal epithelial cells of the intestine, and the lymph and venous systems. The current study suggests that the standard therapy supply almost enough Cu for patient tissues. But given Cu passes through the tissues to venous and lymph systems, or accumulate in the cells responsible for Cu absorption.
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DOI：
10.1016/s1474-4422(14)70190-5
发表时间：
2015-01
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Bandmann O;Weiss KH;Kaler SG
通讯作者：
Kaler SG
影响因子：
4.1
作者：
CAMAKARIS, J;MANN, JR;DANKS, DM
通讯作者：
DANKS, DM
影响因子：
5.2
作者：
Tumer, Zeynep;Moller, Lisbeth B.
通讯作者：
Moller, Lisbeth B.
影响因子：
4.2
作者：
Gupta A;Lutsenko S
通讯作者：
Lutsenko S
影响因子：
17.1
作者：
Iliff JJ;Wang M;Liao Y;Plogg BA;Peng W;Gundersen GA;Benveniste H;Vates GE;Deane R;Goldman SA;Nagelhus EA;Nedergaard M
通讯作者：
Nedergaard M