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Metal Ions in Life Sciences 2013Copper is an essential trace metal that is required for the catalysis of several important cellular enzymes. However, since an excess of copper can also harm cells due... (Review)
Review
Copper is an essential trace metal that is required for the catalysis of several important cellular enzymes. However, since an excess of copper can also harm cells due to its potential to catalyze the generation of toxic reactive oxygen species, transport of copper and the cellular copper content are tightly regulated. This chapter summarizes the current knowledge on the importance of copper for cellular processes and on the mechanisms involved in cellular copper uptake, storage and export. In addition, we will give an overview on disturbances of copper homeostasis that are characterized by copper overload or copper deficiency or have been connected with neurodegenerative disorders.
Topics: Animals; Copper; Ion Transport; Male; Neurodegenerative Diseases; Reactive Oxygen Species
PubMed: 24470097
DOI: 10.1007/978-94-007-7500-8_11 -
Journal of Experimental & Clinical... Sep 2022Elesclomol is an anticancer drug that targets mitochondrial metabolism. In the past, elesclomol was recognized as an inducer of oxidative stress, but now it has also... (Review)
Review
Elesclomol is an anticancer drug that targets mitochondrial metabolism. In the past, elesclomol was recognized as an inducer of oxidative stress, but now it has also been found to suppress cancer by inducing cuproptosis. Elesclomol's anticancer activity is determined by the dependence of cancer on mitochondrial metabolism. The mitochondrial metabolism of cancer stem cells, cancer cells resistant to platinum drugs, proteasome inhibitors, molecularly targeted drugs, and cancer cells with inhibited glycolysis was significantly enhanced. Elesclomol exhibited tremendous toxicity to all three kinds of cells. Elesclomol's toxicity to cells is highly dependent on its transport of extracellular copper ions, a process involved in cuproptosis. The discovery of cuproptosis has perfected the specific cancer suppressor mechanism of elesclomol. For some time, elesclomol failed to yield favorable results in oncology clinical trials, but its safety in clinical application was confirmed. Research progress on the relationship between elesclomol, mitochondrial metabolism and cuproptosis provides a possibility to explore the reapplication of elesclomol in the clinic. New clinical trials should selectively target cancer types with high mitochondrial metabolism and attempt to combine elesclomol with platinum, proteasome inhibitors, molecularly targeted drugs, or glycolysis inhibitors. Herein, the particular anticancer mechanism of elesclomol and its relationship with mitochondrial metabolism and cuproptosis will be presented, which may shed light on the better application of elesclomol in clinical tumor treatment.
Topics: Copper; Humans; Hydrazines; Ionophores; Neoplasms; Platinum; Proteasome Inhibitors
PubMed: 36089608
DOI: 10.1186/s13046-022-02485-0 -
Cell Research May 2022
Topics: Cell Death; Copper; Mitochondria; Apoptosis
PubMed: 35354936
DOI: 10.1038/s41422-022-00653-7 -
Current Opinion in Immunology Oct 2019Transition metal ions are essential to bacterial pathogens and their hosts alike but are harmful in excess. In an effort to curtail the replication of intracellular... (Review)
Review
Transition metal ions are essential to bacterial pathogens and their hosts alike but are harmful in excess. In an effort to curtail the replication of intracellular bacteria, host phagocytes exploit both the essentiality and toxicity of transition metals. In the paradigmatic description of nutritional immunity, iron and manganese are withheld from phagosomes to starve microbial invaders of these nutrients. Conversely, the destructive properties of copper and zinc appear to be harnessed by phagocytes, where these metals are delivered in excess to phagosomes to intoxicate internalized bacteria. Here, we briefly summarize key players in metal withholding from intracellular pathogens, before focusing on recent findings supporting the function of copper and zinc as phagocyte antimicrobial effectors. The mechanisms of copper and zinc toxicity are explored, along with strategies employed by intracellular bacterial pathogens to avoid killing by these metals.
Topics: Anti-Bacterial Agents; Bacteria; Copper; Phagocytes; Zinc
PubMed: 31063946
DOI: 10.1016/j.coi.2019.04.002 -
Journal of Biological Inorganic... Sep 2022Copper is essential in cells as a cofactor for key redox enzymes. Bacteria have acquired molecular components that sense, uptake, distribute, and expel copper ensuring... (Review)
Review
Copper is essential in cells as a cofactor for key redox enzymes. Bacteria have acquired molecular components that sense, uptake, distribute, and expel copper ensuring that cuproenzymes are metallated and steady-state metal levels are maintained. Toward preventing deleterious reactions, proteins bind copper ions with high affinities and transfer the metal via ligand exchange, warranting that copper ions are always complexed. Consequently, the directional copper distribution within cell compartments and across cell membranes requires specific dynamic interactions and metal exchange between cognate holo-apo protein partners. These metal exchange reactions are determined by thermodynamic and kinetics parameters and influenced by mass action. Then, copper distribution can be conceptualized as a molecular system of singular interacting elements that maintain a physiological copper homeostasis. This review focuses on the impact of copper high-affinity binding and exchange reactions on the homeostatic mechanisms, the conceptual models to describe the cell as a homeostatic system, the various molecule functions that contribute to copper homeostasis, and the alternative system architectures responsible for copper homeostasis in model bacteria.
Topics: Bacteria; Chelating Agents; Copper; Homeostasis; Kinetics; Thermodynamics
PubMed: 35802193
DOI: 10.1007/s00775-022-01947-2 -
Annual Review of Microbiology Oct 2021Competition shapes evolution. Toxic metals and metalloids have exerted selective pressure on life since the rise of the first organisms on the Earth, which has led to... (Review)
Review
Competition shapes evolution. Toxic metals and metalloids have exerted selective pressure on life since the rise of the first organisms on the Earth, which has led to the evolution and acquisition of resistance mechanisms against them, as well as mechanisms to weaponize them. Microorganisms exploit antimicrobial metals and metalloids to gain competitive advantage over other members of microbial communities. This exerts a strong selective pressure that drives evolution of resistance. This review describes, with a focus on arsenic and copper, how microorganisms exploit metals and metalloids for predation and how metal- and metalloid-dependent predation may have been a driving force for evolution of microbial resistance against metals and metalloids.
Topics: Copper; Metalloids
PubMed: 34343021
DOI: 10.1146/annurev-micro-032921-123231 -
Chinese Medical Journal Jul 2023Copper plays an important role in many metabolic activities in the human body. Copper level in the human body is in a state of dynamic equilibrium. Recent research on... (Review)
Review
Copper plays an important role in many metabolic activities in the human body. Copper level in the human body is in a state of dynamic equilibrium. Recent research on copper metabolism has revealed that copper dyshomeostasis can cause cell damage and induce or aggravate some diseases by affecting oxidative stress, proteasome, cuprotosis, and angiogenesis. The liver plays a central role in copper metabolism in the human body. Research conducted in recent years has unraveled the relationship between copper homeostasis and liver diseases. In this paper, we review the available evidence of the mechanism by which copper dyshomeostasis promotes cell damage and the development of liver diseases, and identify the future research priorities.
Topics: Humans; Copper; Homeostasis; Oxidative Stress; Liver Diseases
PubMed: 37284739
DOI: 10.1097/CM9.0000000000002697 -
Biomedicine & Pharmacotherapy =... Dec 2023Copper-induced cell death, also known as cuproptosis, is distinct from other types of cell death such as apoptosis, necrosis, and ferroptosis. It can trigger the... (Review)
Review
Copper-induced cell death, also known as cuproptosis, is distinct from other types of cell death such as apoptosis, necrosis, and ferroptosis. It can trigger the accumulation of lethal reactive oxygen species, leading to the onset and progression of aging. The significant increases in copper ion levels in the aging populations confirm a close relationship between copper homeostasis and vascular aging. On the other hand, vascular aging is also closely related to the occurrence of various cardiovascular diseases throughout the aging process. However, the specific causes of vascular aging are not clear, and different living environments and stress patterns can lead to individualized vascular aging. By exploring the correlations between copper-induced cell death and vascular aging, we can gain a novel perspective on the pathogenesis of vascular aging and enhance the prognosis of atherosclerosis. This article aims to provide a comprehensive review of the impacts of copper homeostasis on vascular aging, including their effects on endothelial cells, smooth muscle cells, oxidative stress, ferroptosis, intestinal flora, and other related factors. Furthermore, we intend to discuss potential strategies involving cuproptosis and provide new insights for copper-related vascular aging.
Topics: Copper; Endothelial Cells; Cell Death; Apoptosis; Homeostasis
PubMed: 37976889
DOI: 10.1016/j.biopha.2023.115839 -
Particle and Fibre Toxicology May 2022Since the introduction of copper based, lead-free frangible (LFF) ammunition to Air Force small arms firing ranges, instructors have reported symptoms including chest...
BACKGROUND
Since the introduction of copper based, lead-free frangible (LFF) ammunition to Air Force small arms firing ranges, instructors have reported symptoms including chest tightness, respiratory irritation, and metallic taste. These symptoms have been reported despite measurements determining that instructor exposure does not exceed established occupational exposure limits (OELs). The disconnect between reported symptoms and exposure limits may be due to a limited understanding of LFF firing byproducts and subsequent health effects. A comprehensive characterization of exposure to instructors was completed, including ventilation system evaluation, personal monitoring, symptom tracking, and biomarker analysis, at both a partially enclosed and fully enclosed range.
RESULTS
Instructors reported symptoms more frequently after M4 rifle classes compared to classes firing only the M9 pistol. Ventilation measurements demonstrated that airflow velocities at the firing line were highly variable and often outside established standards at both ranges. Personal breathing zone air monitoring showed exposure to carbon monoxide, ultrafine particulate, and metals. In general, exposure to instructors was higher at the partially enclosed range compared to the fully enclosed range. Copper measured in the breathing zone of instructors, on rare occasions, approached OELs for copper fume (0.1 mg/m). Peak carbon monoxide concentrations were 4-5 times higher at the partially enclosed range compared to the enclosed range and occasionally exceeded the ceiling limit (125 ppm). Biological monitoring showed that lung function was maintained in instructors despite respiratory symptoms. However, urinary oxidative stress biomarkers and urinary copper measurements were increased in instructors compared to control groups.
CONCLUSIONS
Consistent with prior work, this study demonstrates that symptoms still occurred despite exposures below OELs. Routine monitoring of symptoms, urinary metals, and oxidative stress biomarkers can help identify instructors who are particularly affected by exposures. These results can assist in guiding protective measures to reduce exposure and protect instructor health. Further, a longitudinal study is needed to determine the long-term health consequences of LFF firing emissions exposure.
Topics: Biomarkers; Carbon Monoxide; Copper; Dust; Environmental Monitoring; Metals; Occupational Exposure; Oxidative Stress
PubMed: 35570273
DOI: 10.1186/s12989-022-00471-0 -
Microbial Biotechnology Mar 2017Industrial biomining has been extensively used for many years to recover valuable metals such as copper, gold, uranium and others. Furthermore, microorganisms involved... (Review)
Review
Industrial biomining has been extensively used for many years to recover valuable metals such as copper, gold, uranium and others. Furthermore, microorganisms involved in these processes can also be used to bioremediate places contaminated with acid and metals. These uses are possible due to the great metal resistance that these extreme acidophilic microorganisms possess. In this review, the most recent findings related to copper resistance mechanisms of bacteria and archaea related to biohydrometallurgy are described. The recent search for novel metal resistance determinants is not only of scientific interest but also of industrial importance, as reflected by the genomic sequencing of microorganisms present in mining operations and the search of those bacteria with extreme metal resistance to improve the extraction processes used by the biomining companies.
Topics: Anti-Infective Agents; Archaea; Bacteria; Copper; Drug Resistance, Microbial; Industrial Microbiology
PubMed: 27790868
DOI: 10.1111/1751-7915.12450