Copper deficiency is a commonly diagnosed problem in cattle around the globe. In Jimma, Ethiopia, 8 zebu (Bos indicus) and 8 zebu ×: Holstein Friesian cross (Bos taurus ×: Bos indicus) heifers were used in an 11-wk study to investigate breed type differences and effects of Cu deficiency on concentrations of trace elements in plasma and edible tissues as well as mRNA expression of Cu-related gen...

The protein affected in Menkes disease, ATP7A, is a copper (Cu)-transporting P-type ATPase that plays an important role in Cu homeostasis, but the full extent of this role has not been defined at a systemic level. Transgenic mice that overexpress the human ATP7A from the chicken beta-actin composite promoter (CAG) were used to further investigate the physiological function of ATP7A. Overexpress...

The copper-transporting P-type ATPases (Cu-ATPases), ATP7A and ATP7B, are essential for the regulation of intracellular copper homeostasis. In this report we describe new roles for glutathione (GSH) and glutaredoxin1 (GRX1) in Cu homeostasis through their regulation of Cu-ATPase activity. GRX1 is a thiol oxidoreductase that catalyzes the reversible reduction of GSH-mixed disulfides to their res...

The mutant strain Long-Evans Cinnamon (LEC) rat, which accumulates copper in the liver because of a mutation in the Atp7b gene, encoding a copper-ATPase, is a model of Wilson disease. It spontaneously develops hepatitis, and subsequently hepatocellular carcinoma and cholangiofibrosis. Excess intracellular copper has been thought to induce DNA damage through reactive oxygen species produced by C...

Wilson disease (WD) (hepatolenticular degeneration) is an autosomal recessive disorder of copper metabolism due to absence or dysfunction of a Cu P-type ATPase which is essential for the transport of copper (Cu) into the bile. The discovery of the gene cation transporting P-type ATPase involved in the copper transport in many tissues was a breakthrough in the understanding of molecular basis of...

The mechanism of copper (Cu) transport into the brain is unclear. This study evaluated the main species and route of Cu transport into the brain using in situ brain perfusion technique, and assessed the levels of mRNA encoding Cu transporters using real time RT-PCR. Free (64)Cu uptake in rat choroid plexus (CP), where the blood-cerebrospinal fluid barrier (BCB) is primarily located, is about 50...

Copper ATPases, in analogy with other members of the P-ATPase superfamily, contain a catalytic headpiece including an aspartate residue reacting with ATP to form a phosphoenzyme intermediate, and transmembrane helices containing cation-binding sites [TMBS (transmembrane metal-binding sites)] for catalytic activation and cation translocation. Following phosphoenzyme formation by utilization of A...

Copper-transporting P-type adenosine triphosphatase (ATP7B) is reportedly associated with platinum drug resistance in various solid carcinomas. However, the impact of ATP7B on platinum drug resistance in non-small cell lung cancer (NSCLC) remains unknown. We investigated ATP7B expression in nine human NSCLC xenografts using real-time polymerase chain reaction (PCR) and immunohistochemistry, and...

Body copper homeostasis is regulated by the liver, which removes excess copper via bile. In Wilson's disease (WD), this function is disrupted due to inactivation of the copper transporter ATP7B resulting in hepatic copper overload. High urinary copper is a diagnostic feature of WD linked to liver malfunction; the mechanism behind urinary copper elevation is not fully understood. Using Positron ...

ATP7B is a P-type ATPase that mediates the efflux of copper. Recent studies have demonstrated that ATP7B regulates the cellular efflux of cisplatin (DDP) and controls sensitivity to the cytotoxic effects of this drug. To determine whether DDP is a substrate for ATP7B, DDP transport was assayed in vesicles isolated from Sf9 cells infected with a baculovirus that expressed either the wild-type AT...