Copper Transporter ATP7A (Copper-Transporting P-Type ATPase/Menkes ATPase) Limits Vascular Inflammation and Aortic Aneurysm Development

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Purification and membrane reconstitution of catalytically active Menkes copper-transporting P-type ATPase (MNK; ATP7A).

The MNK (Menkes disease protein; ATP7A) is a major copper- transporting P-type ATPase involved in the delivery of copper to cuproenzymes in the secretory pathway and the efflux of excess copper from extrahepatic tissues. Mutations in the MNK (ATP7A) gene result in Menkes disease, a fatal neurodegenerative copper deficiency disorder. Currently, detailed biochemical and biophysical analyses of MN...

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Copper stabilizes the Menkes copper-transporting ATPase (Atp7a) protein expressed in rat intestinal epithelial cells.

Iron deficiency decreases oxygen tension in the intestinal mucosa, leading to stabilization of hypoxia-inducible transcription factor 2α (Hif2α) and subsequent upregulation of genes involved in iron transport [e.g., divalent metal transporter (Dmt1) and ferroportin 1 (Fpn1)]. Iron deprivation also alters copper homeostasis, reflected by copper accumulation in the intestinal epithelium and induc...

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Intracellular targeting of copper-transporting ATPase ATP7A in a normal and Atp7b

Rachel Linz,* Natalie L. Barnes,* Adriana M. Zimnicka, Jack H. Kaplan, Betty Eipper, and Svetlana Lutsenko Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, Oregon; Department of Biochemistry and Molecular Genetics, University of Illinois, Chicago, Illinois; and Department of Neuroscience, University of Connecticut Health Center, Farmington, Conne...

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Intracellular targeting of copper-transporting ATPase ATP7A in a normal and Atp7b-/- kidney.

Kidneys regulate their copper content more effectively than many other organs in diseases of copper deficiency or excess. We demonstrate that two copper-transporting ATPases, ATP7A and ATP7B, contribute to this regulation. ATP7A is expressed, to a variable degree, throughout the kidney and shows age-dependent intracellular localization. In 2-wk-old mice, ATP7A is located in the vicinity of the ...

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A role for the ATP7A copper-transporting ATPase in macrophage bactericidal activity.

Copper is an essential micronutrient that is necessary for healthy immune function. This requirement is underscored by an increased susceptibility to bacterial infection in copper-deficient animals; however, a molecular understanding of its importance in immune defense is unknown. In this study, we investigated the effect of proinflammatory agents on copper homeostasis in RAW264.7 macrophages. ...

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ژورنال

عنوان ژورنال: Arteriosclerosis, Thrombosis, and Vascular Biology

سال: 2019

ISSN: 1079-5642,1524-4636

DOI: 10.1161/atvbaha.119.313374