Copper signaling in the brain and beyond

Ackerman, Cheri M.; Chang, Christopher J.

doi:10.1074/jbc.r117.000176

Cited by 150 publications

(129 citation statements)

References 96 publications

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“…Squitti et al (2002) and Brewer et al (2010b) attribute the dysregulation of copper in the brains of AD patients to an increase in the "labile" or exchangeable pool of copper in peripheral circulation as represented by nonceruloplasmin copper. However, the exact chemical nature of this "labile" pool has remained undefined (Ackerman and Chang 2018). Ceruloplasmin is the main copper carrier in plasma (Harris et al 1999), although many other proteins such as albumin have high bind affinity and capacity for copper and provide reserve binding capacity to keep extracellular ionic copper low.…”

Section: Neurological Disordersmentioning

confidence: 99%

Critical Review of Exposure and Effects: Implications for Setting Regulatory Health Criteria for Ingested Copper

Taylor

Tsuji

Garry

et al. 2019

Environmental Management

382

146

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Decades of study indicate that copper oral exposures are typically not a human health concern. Ingesting high levels of soluble copper salts can cause acute gastrointestinal symptoms and, in uncommon cases, liver toxicity in susceptible individuals with repeated exposure. This focused toxicological review evaluated the current literature since the last comprehensive reviews (2007)(2008)(2009)(2010). Our review identified limitations in the existing United States and international guidance for determining an oral reference dose (RfD) for essential metals like copper. Instead, an alternative method using categorical regression analysis to develop an optimal dose that considers deficiency, toxicity, and integrates information from human and animal studies was reviewed for interpreting an oral RfD for copper. We also considered subchronic

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Section: Neurological Disordersmentioning

confidence: 99%

Critical Review of Exposure and Effects: Implications for Setting Regulatory Health Criteria for Ingested Copper

Taylor

Tsuji

Garry

et al. 2019

Environmental Management

382

146

View full text Add to dashboard Cite

show abstract

“…Copper and copper-dependent proteins are emerging therapeutic targets due to their involvement in cell proliferation, survival, angiogenesis, and metastasis (9,10). Elevated levels of copper in blood and tumor tissue of patients with cancer are correlated with disease progression (11).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Copper Transport Induces Apoptosis in Triple-Negative Breast Cancer Cells and Suppresses Tumor Angiogenesis

Karginova

Weekley

Raoul

et al. 2019

Molecular Cancer Therapeutics

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Treatment of advanced breast cancer remains challenging. Copper and some of the copper-dependent proteins are emerging therapeutic targets because they are essential for cell proliferation and survival, and have been shown to stimulate angiogenesis and metastasis. Here, we show that DCAC50, a recently developed small-molecule inhibitor of the intracellular copper chaperones, ATOX1 and CCS, reduces cell proliferation and elevates oxidative stress, triggering apoptosis in a panel of triple-negative breast cancer (TNBC) cells. Inhibition of ATOX1 activity with DCAC50 disrupts copper homeostasis, leading to increased copper levels, altered spatial copper redistribution, and accumula-tion of ATP7B to the cellular perinuclear region. The extent and impact of this disruption to copper homeostasis vary across cell lines and correlate with cellular baseline copper and glutathione levels. Ultimately, treatment with DCAC50 attenuates tumor growth and suppresses angiogenesis in a xenograft mouse model, and prevents endothelial cell network formation in vitro. Co-treatment with paclitaxel and DCAC50 enhances cytotoxicity in TNBC and results in favorable dose reduction of both drugs. These data demonstrate that inhibition of intracellular copper transport targets tumor cells and the tumor microenvironment, and is a promising approach to treat breast cancer.

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“…In mammals, about two dozen enzymes, which control the basic cellular processes: respiration, antioxidant defense, formation of connective tissue, neurotransmitter synthesis, neuropeptide processing, iron transport and others, require copper as a co-factor for their activity [10,11]. Moreover, copper operates as a secondary messenger in some signaling ways [12]. In adult mammals, copper deficiency or excess of copper from dietary factors are rarely observed.…”

Section: Introductionmentioning

confidence: 99%

Copper Metabolism of Newborns Is Adapted to Milk Ceruloplasmin As a Nutritive Source of Copper

Puchkova¹,

Babich²,

Zatulovskaia³

et al. 2018

Preprint

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Copper, which can potentially be a highly toxic agent, is an essential nutrient due to its role as a co-factor for cuproenzymes and participation in signaling pathways. In mammals, the liver is a central organ that controls copper turnover throughout the body: copper absorption, distribution, and excretion. In ontogenesis, there are two types of copper metabolism: embryonic and adult, which maintain the balance of copper in each of these periods, respectively. In the liver cells, these types are characterized by specific expression patterns and activity levels of the genes encoding ceruloplasmin, which is the main extracellular ferroxidase and copper transporter and proteins mediating ceruloplasmin metalation. In newborns, the molecular-genetic mechanisms responsible for copper homeostasis and the ontogenetic switch from embryonic to adult copper metabolism are highly adapted to milk ceruloplasmin as a dietary source of copper. In the mammary gland cells, the level of ceruloplasmin gene expression and the alternative splicing of its pre-mRNA govern the amount of ceruloplasmin in milk, and thus, the amount of copper absorbed by the newborn is controlled. In the newborns, absorption, distribution, and accumulation copper are adapted to milk ceruloplasmin. In the newborns, which are not breast-fed at the early stages of postnatal development, the control for alimentary copper balance is absent. We tried to focus on the neonatal consequences of a violation of the balance of copper in the mother / newborn system. Although there is still much to be learned, the time to pay attention to this problem came because the neonatal misbalance of copper may provoke the development of copper related disorders for future life.

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Copper signaling in the brain and beyond

Cited by 150 publications

References 96 publications

Critical Review of Exposure and Effects: Implications for Setting Regulatory Health Criteria for Ingested Copper

Critical Review of Exposure and Effects: Implications for Setting Regulatory Health Criteria for Ingested Copper

Inhibition of Copper Transport Induces Apoptosis in Triple-Negative Breast Cancer Cells and Suppresses Tumor Angiogenesis

Copper Metabolism of Newborns Is Adapted to Milk Ceruloplasmin As a Nutritive Source of Copper

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