Diagnostic copper imaging of Menkes disease by synchrotron radiation-generated X-ray fluorescence analysis

Miyuki Kinebuchi, Akihiro Matsuura, Tohru Kiyono, Yumiko Nomura, Sachiko Kimura

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number33247
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 15-09-2016

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Menkes Kinky Hair Syndrome
Synchrotrons
Lymph
Diagnostic Imaging
Copper
Fluorescence
X-Rays
Radiation
Human Development
Histidine
Oxidation-Reduction
Intestines
Adenosine Triphosphatases
Spinal Cord
Central Nervous System
Epithelial Cells
Metals
Cell Membrane
Kidney
Mutation

All Science Journal Classification (ASJC) codes

  • General

Cite this

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abstract = "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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Diagnostic copper imaging of Menkes disease by synchrotron radiation-generated X-ray fluorescence analysis. / Kinebuchi, Miyuki; Matsuura, Akihiro; Kiyono, Tohru; Nomura, Yumiko; Kimura, Sachiko.

In: Scientific Reports, Vol. 6, 33247, 15.09.2016.

Research output: Contribution to journalArticle

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