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Copper imbalance

Guenter Weiss, Peggy L Carver
BACKGROUND: Divalent metals play important roles in maintaining metabolism and cellular growth of both eukaryotic hosts and invading microbes. Both metal deficiency and overload can result in abnormal cellular function or damage. Given its central role in host pathogen interactions, subtle alterations of divalent metal homeostasis occur in the course of infectious diseases which aim, from the host perspective, either to reduce the availability of respective metals to microbes, or to use toxic metal accumulation to eliminate pathogens...
January 28, 2017: Clinical Microbiology and Infection
Fang Xie, Yin Xi, Juan M Pascual, Otto Muzik, Fangyu Peng
Copper is a nutritional metal required for brain development and function. Wilson's disease (WD), or hepatolenticular degeneration, is an inherited human copper metabolism disorder caused by a mutation of the ATP7B gene. Many WD patients present with variable neurological and psychiatric symptoms, which may be related to neurodegeneration secondary to copper metabolism imbalance. The objective of this study was to explore the feasibility and use of copper-64 chloride ([(64)C]CuCl2) as a tracer for noninvasive assessment of age-dependent changes of cerebral copper metabolism in WD using an Atp7b (-/-) knockout mouse model of WD and positron emission tomography/computed tomography (PET/CT) imaging...
January 27, 2017: Metabolic Brain Disease
Priyanka Chauhan, Sai Brinda Muralidharan, Anand Babu Velappan, Dhrubajyoti Datta, Sanjay Pratihar, Joy Debnath, Kalyan Sundar Ghosh
Protein aggregation, due to the imbalance in the concentration of Cu(2+) and Zn(2+) ions is found to be allied with various physiological disorders. Copper is known to promote the oxidative damage of β/γ-crystallins in aged eye lens and causes their aggregation leading to cataract. Therefore, synthesis of a small-molecule 'chelator' for Cu(2+) with complementary antioxidant effect will find potential applications against aggregation of β/γ-crystallins. In this paper, we have reported the synthesis of different Schiff bases and studied their Cu(2+) complexation ability (using UV-Vis, FT-IR and ESI-MS) and antioxidant activity...
January 5, 2017: Journal of Biological Inorganic Chemistry: JBIC
Priyatosh Ranjan, Dhiman Ghosh, Deepthi S Yarramala, Subhadeep Das, Samir K Maji, Ashutosh Kumar
BACKGROUND: Copper is an essential trace element required for the proper functioning of various enzymes present in the central nervous system. An imbalance in the copper homeostasis results in the pathology of various neurodegenerative disorders including Parkinson's Disease. Hence, residue specific interaction of Cu(2+) to α-Syn along with the familial mutants H50Q and G51D needs to be studied in detail. METHODS: We investigated the residue specific mapping of Cu(2+) binding sites and binding strength using solution-state NMR and ITC respectively...
February 2017: Biochimica et Biophysica Acta
Pu Wang, Zhan-You Wang
Alzheimer's disease (AD) is a common form of dementia in aged people, which is defined by two pathological characteristics: β-amyloid protein (Aβ) deposition and tau hyperphosphorylation. Although the mechanisms of AD development are still being debated, a series of evidence supports the idea that metals, such as copper, iron, zinc, magnesium and aluminium, are involved in the pathogenesis of the disease. In particular, the processes of Aβ deposition in senile plaques (SP) and the inclusion of phosphorylated tau in neurofibrillary tangles (NFTs) are markedly influenced by alterations in the homeostasis of the aforementioned metal ions...
November 6, 2016: Ageing Research Reviews
Gangapatnam Subrahmanyam, Rama Mohan Pathapati, Krishnan Ramalingam, Selvam Armugam Indira, Katari Kantha, Bhemasen Soren
INTRODUCTION: Stiffening of arteries is a natural ageing process. Any diseases/disorders or risk factors that escalate oxidative stress, microvascular inflammation and endothelial damage may promote to premature vascular stiffening. Any imbalance in these trace element levels may independently contribute to the changes in the components in the arterial wall and thus, arterial stiffness via one or more mechanisms. AIM: To evaluate the severity of arterial stiffness in apparently healthy population and also to evaluate role of various risk factors and trace elements in the severity of arterial stiffness...
September 2016: Journal of Clinical and Diagnostic Research: JCDR
Somayeh Atari-Hajipirloo, Neda Valizadeh, Mohammad-Hassan Khadem-Ansari, Yousef Rasmi, Fatemeh Kheradmand
BACKGROUND: The altered levels of some essential trace elements and antioxidant minerals have been observed in diabetic patients. OBJECTIVES: The aim of the present study was to compare the concentrations of essential trace elements, copper (Cu), zinc (Zn), and iron (Fe) in the serum of patients who have type 2 diabetes mellitus (T2DM) with those of their non-diabetic first-degree relatives (FDR) and control subjects. The association between glycated hemoglobin (HbA1c) and levels of metals was also evaluated...
April 2016: International Journal of Endocrinology and Metabolism
Caroline Reynaud, Laura Ferreras, Paola Di Mauro, Casina Kan, Martine Croset, Edith Bonnelye, Floriane Pez, Clémence Thomas, Géraldine Aimond, Antoine E Karnoub, Marie Brevet, Philippe Clézardin
Lysyl oxidase (LOX) is a secreted copper-dependent amine oxidase whose primary function is to drive collagen crosslinking and extracellular matrix stiffness. LOX in colorectal cancer synergizes with hypoxia-inducible factor-1 (HIF-1) to promote tumor progression. Here we investigated whether LOX/HIF1 endows colorectal cancer cells with full competence for aggressive colonization in bone. We show that a high LOX expression in primary tumors from patients with colorectal cancer was associated with poor clinical outcome, irrespective of HIF-1 In addition, LOX was expressed by tumor cells in the bone marrow from colorectal cancer patients with bone metastases...
January 15, 2017: Cancer Research
Kaushik Banerjee, Satyajit Das, Avijit Sarkar, Mitali Chatterjee, Jaydip Biswas, Soumitra Kumar Choudhuri
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive form of cancer and the therapeutic outcome for T-ALL patients remains poor. Thus innovative therapeutic strategies with less toxic drugs are of immense need. Moreover combinational effect of redox imbalance with modulated EGFR/PI3K/Akt axis in T-ALL is still elusive. To explore more effective drugs we developed and characterized 5-SMAG, Cu-5-SMAG and Cu-OBPHA complexes by different spectroscopic methods and revealed that introduction of methoxy group and copper to the previously synthesized Schiff base ligand, NG can efficiently target leukemia by sparing the normal cells and overcomes MDR in T-ALL through induction of caspase3 dependent apoptosis as assessed by MTT, Cell-cycle, Annexin-V and caspase3 activation assay...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Raşit Kılıç, Aslhan Cavunt Bayraktar, Serdar Bayraktar, Ali Kurt, Mustafa Kavutçu
PURPOSE: The aim of this study was to evaluate the relationship between antioxidant superoxide dismutase (SOD) enzyme activity, malondialdehyde (MDA) as a lipid peroxidation marker, and some trace elements such as zinc (Zn) and copper (Cu) levels in patients with keratoconus. METHODS: A total of 58 patients with keratoconus and 53 control subjects with similar age and sex were evaluated in this study. The modified Krumeich keratoconus classification was used to divide the patients into 4 stages...
December 2016: Cornea
M A Greenough
An imbalance in metal homeostasis is a prominent feature of Alzheimer's disease (AD). A wealth of evidence from independent studies over the past two and half decades has found changes to the distribution of brain iron, zinc, and copper in AD patients and animal models of the disease. Early research focused on the association of these metals with amyloid beta (Aβ), particularly extraneuronal Aβ plaque pathology. In contrast, there are numerous studies that have demonstrated a loss of iron-, zinc-, or copper-dependent cellular functions in AD animal and cell models, highlighting the importance of metal homeostasis in maintaining healthy brain function...
November 2016: Journal of Molecular Neuroscience: MN
S A Beigh, J S Soodan, A M Bhat
The present study was aimed to determine the effect on liver, associated oxidative stress, trace element and vitamin alteration in dogs with sarcoptic mange. A total of 24 dogs with clinically established diagnosis of sarcoptic mange, divided into two groups, severely infested group (n=9) and mild/moderately infested group (n=15), according to the extent of skin lesions caused by sarcoptic mange and 6 dogs as control group were included in the present study. In comparison to healthy control hemoglobin, PCV, and TEC were significantly (P<0...
August 30, 2016: Veterinary Parasitology
Elaine Hilário-Souza, Martine Cuillel, Elisabeth Mintz, Peggy Charbonnier, Adalberto Vieyra, Doris Cassio, Jennifer Lowe
Different studies have revealed copper imbalance in individuals suffering from diabetes and obesity, suggesting that regulation of glucose and/or fat metabolism could modulate cellular copper homeostasis. To test this hypothesis we investigated whether the key hormones of energy metabolism, insulin and glucagon, regulate the functional properties of the major hepatic copper-transporter, ATP7B (i.e., copper-dependent ATPase activity). We demonstrated that insulin reverses the effect of copper and stimulates retrograde trafficking of ATP7B from the canalicular membranes, consistent with the enhanced ability of ATP7B to sequester copper away from the cytosol...
November 2016: Biochimica et Biophysica Acta
Moslem Shaabani, Yones Lotfi, Seyed Morteza Karimian, Mehdi Rahgozar, Mehdi Hooshmandi
Current experimental research on the therapeutic effects of galvanic vestibular stimulation (GVS) has mainly focused on neurodegenerative disorders. However, it primarily stimulates the vestibular nuclei and could be potentially effective in modulating imbalance between them in the case of unilateral labyrinthectomy (UL). Fifty male Wistar rats (180-220g) were used in 5 groups of 10: intact, sham, right-UL (RUL; without intervention), and two other right-UL groups with GVS intervention [one group treated with low rate GVS (GVS...
October 1, 2016: Brain Research
Manon Gault, Géraldine Effantin, Agnès Rodrigue
The biology of nickel has been widely studied in mammals because of its carcinogenic properties, whereas few studies have been performed in microorganisms. In the present work, changes accompanying stress caused by nickel were evaluated at the cellular level using RNA-Seq in Escherichia coli K-12. Interestingly, a very large number of genes were found to be deregulated by Ni stress. Iron and oxidative stress homeostasis maintenance were among the most highly enriched functional categories, and genes involved in periplasmic copper efflux were among the most highly upregulated...
August 2016: Free Radical Biology & Medicine
Amber Lothian, Blaine R Roberts
Metals are essential for protein function as cofactors to catalyze chemical reactions. Disruption of metal homeostasis is implicated in a number of diseases including Alzheimer's and Parkinson's disease, but the exact role these metals play is yet to be fully elucidated. Identification of metalloproteins encounters many challenges and difficulties. Here we report an approach that allows metalloproteins in complex samples to be quantified. This is achieved using size exclusion chromatography coupled with inductively coupled plasma - mass spectrometry (SEC-ICP-MS)...
2016: Journal of Visualized Experiments: JoVE
Pedro Humberto Castro, Nuno Verde, Rui Manuel Tavares, Eduardo Rodríguez Bejarano, Herlânder Azevedo
SUMO is a modifying peptide that regulates protein activity and is essential to eukaryotes. In plants, SUMO plays an important role in both development and the response to environmental stimuli. The best described sumoylation pathway component is the SUMO E3 ligase SIZ1. Its mutant displays inefficient responses to nutrient imbalance in phosphate, nitrate and copper. Recently, we reported that siz1 also displays altered responses to exogenous sugar supplementation. The siz1 mutant is a salicylic acid (SA) accumulator, and SA may interfere with sugar-dependent responses and signaling events...
May 2, 2016: Plant Signaling & Behavior
Ana B Caballero, Laia Terol-Ordaz, Alba Espargaró, Guillem Vázquez, Ernesto Nicolás, Raimon Sabaté, Patrick Gamez
Brain copper imbalance plays an important role in amyloid-β aggregation, tau hyperphosphorylation, and neurotoxicity observed in Alzheimer's disease (AD). Therefore, the administration of biocompatible metal-binding agents may offer a potential therapeutic solution to target mislocalized copper ions and restore metallostasis. Histidine-containing peptides and proteins are excellent metal binders and are found in many natural systems. The design of short peptides showing optimal binding properties represents a promising approach to capture and redistribute mislocalized metal ions, mainly due to their biocompatibility, ease of synthesis, and the possibility of fine-tuning their metal-binding affinities in order to suppress unwanted competitive binding with copper-containing proteins...
May 17, 2016: Chemistry: a European Journal
P Stehle, B Stoffel-Wagner, K S Kuhn
The aim of this systematic review (PubMed, and Cochrane,; last entry 31 December 2014) was to present data from recent clinical studies investigating parenteral trace element provision in adult patients and to draw conclusions for clinical practice. Important physiological functions in human metabolism are known for nine trace elements: selenium, zinc, copper, manganese, chromium, iron, molybdenum, iodine and fluoride. Lack of, or an insufficient supply of, these trace elements in nutrition therapy over a prolonged period is associated with trace element deprivation, which may lead to a deterioration of existing clinical symptoms and/or the development of characteristic malnutrition syndromes...
August 2016: European Journal of Clinical Nutrition
Alzbeta Ressnerova, Martina Raudenska, Monika Holubova, Marketa Svobodova, Hana Polanska, Petr Babula, Michal Masarik, Jaromir Gumulec
Metals are known for playing essential roles in human physiology. Copper and zinc are trace elements closely dependent on one another and are involved in cell proliferation, growth, gene expression, apoptosis and other processes. Their homeostasis is crucial and tightly controlled by a resourceful system of transporters and transport proteins which deliver copper and zinc ions to their target sites. Abnormal zinc and copper homeostasis can be seen in a number of malignancies and also in head and neck cancer...
2016: Current Medicinal Chemistry
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