The copper transport protein Atox1 promotes neuronal survival

被引:71
作者
Kelner, GS
Lee, MH
Clark, ME
Maciejewski, D
McGrath, D
Rabizadeh, S
Lyons, T
Bredesen, D
Jenner, P
Maki, RA
机构
[1] Neurocrine Biosci, Dept Mol Biol, San Diego, CA 92121 USA
[2] Kings Coll London, London SW3 6LX, England
[3] Burnham Inst, La Jolla, CA 92037 USA
[4] Buck Ctr Res Aging, Novato, CA 94948 USA
关键词
D O I
10.1074/jbc.275.1.580
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:580 / 584
页数:5
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