title: The copper transport protein Atox1 promotes neuronal survival.
abstract: Atox1, a copper transport protein, was recently identified as a copper-dependent suppressor of oxidative damage in yeast lacking superoxide dismutase. We have previously reported that Atox1 in the rat brain is primarily expressed in neurons, with the highest levels in distinct neuronal subtypes that are characterized by their high levels of metal, like copper, iron, and zinc. In this report, we have transfected the Atox1 gene into several neuronal cell lines to increase the endogenous level of Atox1 expression and have demonstrated that, under conditions of serum starvation and oxidative injury, the transfected neurons are significantly protected against this stress. This level of protection is comparable with the level of protection seen with copper/zinc superoxide dismutase and the anti-apoptotic gene bcl-2 that had been similarly transfected. Furthermore, neuronal cell lines transfected with a mutant Atox1 gene, where the copper binding domain has been modified to prevent metal binding, do not afford protection against serum starvation resulting in apoptosis. Therefore, Atox1 is a component of the cellular pathways used for protection against oxidative stress.
authors.affiliation: Department of Molecular Biology, Neurocrine Biosciences, San Diego, California 92121, USA.
authors.forename: G S
authors.initials: GS
authors.lastname: Kelner
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: M E
authors.initials: ME
authors.lastname: Clark
authors.forename: D
authors.initials: D
authors.lastname: Maciejewski
authors.forename: D
authors.initials: D
authors.lastname: McGrath
authors.forename: S
authors.initials: S
authors.lastname: Rabizadeh
authors.forename: T
authors.initials: T
authors.lastname: Lyons
authors.forename: D
authors.initials: D
authors.lastname: Bredesen
authors.forename: P
authors.initials: P
authors.lastname: Jenner
authors.forename: R A
authors.initials: RA
authors.lastname: Maki
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins; D002470:Cell Survival; D003001:Cloning, Molecular; D003300:Copper / Q000378:metabolism*; D000079922:Copper Transport Proteins; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
chemical_list: C499248:Atox1 protein, rat; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D000079922:Copper Transport Proteins; D018832:Molecular Chaperones; D009479:Neuropeptides; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D003300:Copper