title: Diagnostic copper imaging of Menkes disease by synchrotron radiation-generated X-ray fluorescence analysis.
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 Cu(2+) 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.
authors.affiliation: Department of Molecular Pathology, Graduate School of Medicine, Fujita Health University, Toyoake, Aichi, 470-1192, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Kinebuchi
authors.affiliation: Department of Molecular Pathology, Graduate School of Medicine, Fujita Health University, Toyoake, Aichi, 470-1192, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Matsuura
authors.affiliation: National Cancer Center Research Institute, 5-1-1Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Kiyono
authors.affiliation: Aomori City Public Health Center, 19-13 Tsukuda 2-chome, Aomori City, Aomori, 030-0962, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Nomura
authors.affiliation: Hokkaido Medical Center for Child Health and Rehabilitation, 240-6 Kanayama 1-jo 1-chome, Teine-ku, Sapporo, Hokkaido, 006-0041, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kimura
mesh_terms: D002490:Central Nervous System / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D003300:Copper / Q000172:deficiency / Q000378:metabolism*; D000073840:Copper-Transporting ATPases / Q000097:blood / Q000235:genetics; D005453:Fluorescence; D006639:Histidine / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007706:Menkes Kinky Hair Syndrome / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D011859:Radiography; D017356:Synchrotrons; D014965:X-Rays
chemical_list: D006639:Histidine; D003300:Copper; C081184:ATP7A protein, human; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases