Copper Efflux from Murine Microvascular Cells Requires Expression of the Menkes Disease Cu-ATPase

Qian, Yongchang; Tiffany‐Castiglioni, Evelyn; Welsh, Jane; Harris, Edward D.

doi:10.1093/jn/128.8.1276

Cited by 66 publications

(40 citation statements)

References 26 publications

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“…Indeed, impairment of synthesis, secretory and transportation functions of the choroid plexus is documented in aging, and worsens in AD (Serot et al 2003). Another copper-transporting ATPase, ATP7A, which is homologous to ATP7B, is present in the choroid plexus and it is thought to control the overall copper supply to the brain (Iwase et al 1996;Qian et al 1998). Therefore, ATP7A may be affected in AD choroids plexus, thus resulting in decreased activity of secreted copper proteins, needs to be ascertained.…”

Section: Discussionmentioning

confidence: 99%

Features of ceruloplasmin in the cerebrospinal fluid of Alzheimer’s disease patients

et al. 2007

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The level of the apo-form of the copper enzyme ceruloplasmin (CP) is an established peripheral marker in diseases associated with copper imbalance. In view of the proposal that disturbances of copper homeostasis may contribute to neurodegeneration associated with Alzheimer's disease (AD), the present work investigates, by Western blot and non-reducing SDS-PAGE followed by activity staining, the features of CP protein, and the copper/CP relationship in cerebrospinal fluid (CSF) and serum of AD patients. Results show that only a fraction of total copper is associated with CP in the CSF, at variance with serum, both in affected and in healthy individuals. Furthermore, a conspicuous amount of apo-ceruloplasmin and a decrease of CP oxidase activity characterize the CSF of the affected individuals, and confirm that an impairment of copper metabolism occurs in their central nervous system. In the CSF of AD patients the decrease of active CP, associated with the increase in the pool of copper not sequestered by this protein, may play a role in the neurodegenerative process.

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Section: Discussionmentioning

confidence: 99%

Features of ceruloplasmin in the cerebrospinal fluid of Alzheimer’s disease patients

et al. 2007

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“…In contrast, Hg specifically targets sulfhydryl or thiol groups of proteins to induce oxidative stress (Guo et al, 1998). Organic mercury, p-chloromer-curibenzoate (PCMB), also blocks copper release from cells (Qian et al, 1995(Qian et al, , 1997(Qian et al, , 1998. The ability of both metals to modulate protein binding activities to GST-Ya ARE/EpRE, NF-~:B, Ha-ras ARE/EpRE, and AP-1 consensus binding sequences raises the intriguing possibility that modulation of grp78 expression by metals involves a transcriptional mechanism mediated by redox-regulated transcription factors, even though some different responses of binding activities to these factors were observed between Pb and Hg-exposed cells (Figs.…”

Section: Discussionmentioning

confidence: 99%

Induction of 78 kD glucose-regulated protein (GRP78) expression and redox-regulated transcription factor activity by lead and mercury in C6 rat glioma cells

et al. 2001

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Lead (Pb) and mercury (Hg) are widespread environmental contaminants that induce prominent neural toxicity. Although the brain is not the major Pb and Hg depot in the body, these metals preferentially accumulate in astroglia to exert toxic effects. In this study, we examined the effects of Pb acetate and HgCl(2) on the expression of GRP78, a molecular chaperone in the endoplasmic reticulum (ER) that may provide cytoprotection in response to cellular stresses in the C6 rat glioma cell line. We also evaluated the DNA binding activities of several redox-regulated transcription factors in metal-treated cells. Our results showed that mRNA levels of GRP78 were up-regulated by Pb and Hg at 0.1 and 1 micro M, but down-regulated at higher concentrations (10 micro M). GRP78 protein levels increased in a concentration- and time-dependent manner in Pb and/or Hg-treated cells. Pb increased protein binding to the GST- Upsilon a antioxidant/electrophile response element (ARE/EpRE) and to the NF- kappaB consensus binding sequence of the cytomegalovirus 2 (CMB2) promoter, but decreased protein binding to the Ha-ras ARE/EpRE or to the c-fos 12-O-tetradecanoyl-phorbol-13-acetate (TPA) response element (TRE). In contrast, Hg activated DNA binding by all redox-regulated transcription factors. These studies shed some light on the molecular mechanisms of Pb and Hg toxicity in C6 rat glioma cells and suggest that GRP78 and oxidative stress may participate in the neurotoxic response to these metals.

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“…This is required to incorporate the ion into cuproenzymes, such as the dopamine-beta-hydroxylase (see Table 1 for the main cuproenzymes). ATP7A is critical to deliver copper from endothelial cells in the direction of the brain [24]. ATP7A is essential not only for the CNS, but also for peripheral nerves [25].…”

Section: The Atpases Atp7a/atp7b Ctr1 and Chaperonesmentioning

confidence: 99%

Abnormal Copper Homeostasis: Mechanisms and Roles in Neurodegeneration

Manto

2014

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As a cofactor of proteins and enzymes involved in critical molecular pathways in mammals and low eukaryotes, copper is a transition metal essential for life. The intra-cellular and extra-cellular metabolism of copper is under tight control, in order to maintain free copper concentrations at very low levels. Copper is a critical element for major neuronal functions, and the central nervous system is a major target of disorders of copper metabolism. Both the accumulation of copper and copper deficiency are associated with brain dysfunction. The redox capacities of free copper, its ability to trigger the production of reactive oxygen species and the close relationships with the regulation of iron and zinc are remarkable features. Major advances in our understanding of the relationships between copper, neuronal functions and neurodegeneration have occurred these last two decades. The metabolism of copper and the current knowledge on the consequences of copper dysregulation on brain disorders are reviewed, with a focus on neurodegenerative diseases, such as Wilson's disease, Alzheimer's disease and Parkinson's disease. In vitro studies, in vivo experiments and evidence from clinical observations of the neurotoxic effects of copper provide the basis for future therapies targeting copper homeostasis.

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Copper Efflux from Murine Microvascular Cells Requires Expression of the Menkes Disease Cu-ATPase

Cited by 66 publications

References 26 publications

Features of ceruloplasmin in the cerebrospinal fluid of Alzheimer’s disease patients

Features of ceruloplasmin in the cerebrospinal fluid of Alzheimer’s disease patients

Induction of 78 kD glucose-regulated protein (GRP78) expression and redox-regulated transcription factor activity by lead and mercury in C6 rat glioma cells

Abnormal Copper Homeostasis: Mechanisms and Roles in Neurodegeneration

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