Expression profile of the copper homeostasis gene, rAtox1, in the rat brain

• Published in: Neuroscience Vol. 93; no. 3; pp. 1179 - 1187
• Main Authors: Naeve, G.S., Vana, A.M., Eggold, J.R., Kelner, G.S., Maki, R., DeSouza, E.B., Foster, A.C.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-08-1999; Elsevier
• Subjects: Animals; Biochemistry and metabolism; Biological and medical sciences; Brain - metabolism; Carrier Proteins - biosynthesis; Carrier Proteins - genetics; Cation Transport Proteins; Central nervous system; ceruloplasmin; copper; Copper - metabolism; DNA, Complementary - genetics; dopamine-β-hydroxylase; Fundamental and applied biological sciences. Psychology; Fungal Proteins - genetics; Gene Expression Regulation; Hippocampus - metabolism; Homeostasis; Humans; In Situ Hybridization; Iron - metabolism; Metallochaperones; Mice; Molecular Chaperones; Organ Specificity; Oxidative Stress; rAtox1 gene; Rats; Saccharomyces cerevisiae Proteins; Species Specificity; Tegmentum Mesencephali - metabolism; Vertebrates: nervous system and sense organs; Zinc - metabolism; ceruloplasmin; DAB, 3,3′-diaminobenzidine hydrochloride; EDTA, ethylenediaminetetra-acetate; ISH, in situ hybridization histochemistry; SSC, standard saline citrate; LC, locus coeruleus; ALS, amyotrophic lateral sclerosis; DTT, dithiothreitol; SOD, superoxide dismutase; dopamine-β-hydroxylase; PBS, phosphate-buffered saline; DBH, dopamine-β-hydroxylase; copper; TCA, trichloroacetic acid; SDS, sodium dodecyl sulphate; Dopamine β-monooxygenase; Rat; Enzyme; Rodentia; Central nervous system; Homeostasis; Gene expression; Vertebrata; Mammalia; Gene; Oxidoreductases; Copper; Brain (vertebrata)
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(99)00175-X

In humans the regulation of cellular copper homeostasis is essential for proper organ development and function. A novel cytosolic protein, named Atox1, was recently identified in yeast that functions in shuttling intracellular mononuclear copper [Cu(I)] to copper-requiring proteins. Atox1 and its human homolog, hAtox1, are members of an emerging family of proteins termed copper chaperones that are involved in the maintenance of copper homeostasis. Northern blot analysis demonstrates that Atox1 is widely expressed at varying levels in a variety of rat tissues including brain. Using
in situ hybridization histochemistry, we characterized the expression profile for the rat homolog of Atox1 (rAtox1) in the normal adult rat brain. There is widespread expression within the brain that appears to be primarily neuronal. The highest levels of Atox1 message consists of distinct neuronal subtypes that are also characterized by their high levels of metals like copper, iron, and zinc, which include the pyramidal neurons of the cerebral cortex and hippocampus in addition to the neurons of the locus coeruleus. The high levels of a metal chaperone like Atox1 in subsets of neurons that also sequester metals suggests that Atox1 may be important in maintaining the functionality of metal requiring enzymes.
A detailed analysis of the restricted expression profile for a novel copper chaperone, rAtox1, is described in the adult rat CNS. Further analysis shows that Atox1 expression is associated with neuronal populations that sequester copper.