title: Zinc transporters ZnT3 and ZnT6 are downregulated in the spinal cords of patients with sporadic amyotrophic lateral sclerosis.
abstract: The loss of homeostasis of essential metals is associated with various diseases, including neurodegenerative diseases. Previous studies have shown that the levels of zinc (Zn) are significantly higher in the cerebrospinal fluid of patients with amyotrophic lateral sclerosis (ALS). Zn transporters and metallothioneins tightly control intracellular and extracellular Zn levels. This study investigated the protein levels of ZnT, a Zn transporter family, in ALS patients and model mice. The mRNA expression of ZnT1, -3, -4, -5, -6, -7, and -10 was assessed in the spinal cords of human control subjects. ZnT3 and ZnT6 protein levels were significantly diminished in the spinal cords of sporadic ALS patients compared with controls. Furthermore, immunohistochemical staining demonstrated decreased ZnT3 and ZnT6 immunoreactivity in the ventral horn of the spinal cords in ALS patients. Moreover, immunohistochemical analysis revealed that all ZnTs expressed in the spinal cords were localized in a distinct subset of motor neurons. In addition, ZnT3 and ZnT6 protein levels were not altered in SOD1 (G93A) mutant transgenic mice before or after the onset of ALS symptoms compared with controls. These results suggest that ZnT3 and ZnT6 protein levels are decreased in the spinal cords of sporadic ALS patients; however, this did not occur merely via loss of motor neurons.
authors.affiliation: Laboratory of Medical Therapeutics and Molecular Therapeutics, Department of Biomedical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kaneko
authors.forename: Takao
authors.initials: T
authors.lastname: Noguchi
authors.forename: Saori
authors.initials: S
authors.lastname: Ikegami
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Sakurai
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Toyoshima
authors.forename: Taiho
authors.initials: T
authors.lastname: Kambe
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Yamada
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Inden
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
authors.forename: Kiyomitsu
authors.initials: K
authors.lastname: Oyanagi
authors.forename: Takashi
authors.initials: T
authors.lastname: Inuzuka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Isao
authors.initials: I
authors.lastname: Hozumi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D012333:RNA, Messenger; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: D027682:Cation Transport Proteins; D012333:RNA, Messenger; C102806:SLC30A3 protein, human; C504822:SLC30A6 protein, human; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase
keywords: ER stress; biometal; immunohistochemistry