Copper homeostasis and copper-induced cell death in the pathogenesis of cardiovascular disease and therapeutic strategies

Cell Death and Disease, Год журнала: 2023, Номер 14(2)

Опубликована: Фев. 11, 2023

Abstract Copper is a vital mineral, and an optimal amount of copper required to support normal physiologic processes in various systems, including the cardiovascular system. Over past few decades, copper-induced cell death, named cuproptosis, has become increasingly recognized as important process mediating pathogenesis progression disease (CVD), atherosclerosis, stroke, ischemia-reperfusion injury, heart failure. Therefore, in-depth understanding regulatory mechanisms cuproptosis CVD may be useful for improving management. Here, we review relationship between homeostasis cuproptosis-related pathways CVD, well therapeutic strategies addressing death CVD.

Язык: Английский

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Copper in cancer: from limiting nutrient to therapeutic target

Frontiers in Oncology, Год журнала: 2023, Номер 13

Опубликована: Июнь 23, 2023

As an essential nutrient, copper’s redox properties are both beneficial and toxic to cells. Therefore, leveraging the characteristics of copper-dependent diseases or using copper toxicity treat copper-sensitive may offer new strategies for specific disease treatments. In particular, concentration is typically higher in cancer cells, making a critical limiting nutrient cell growth proliferation. Hence, intervening metabolism cells become potential tumor treatment strategy, directly impacting metastasis. this review, we discuss body summarize research progress on role promoting inducing programmed death Additionally, elucidate copper-related drugs treatment, intending provide perspectives treatment.

Язык: Английский

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Copper Homeostasis in Chronic Kidney Disease and Its Crosstalk with Ferroptosis

Pharmacological Research, Год журнала: 2024, Номер 202, С. 107139 - 107139

Опубликована: Март 12, 2024

Chronic kidney disease (CKD) has become a global public health problem with high morbidity and mortality. Renal fibrosis can lead to end-stage renal (ESRD). However, there is still no effective treatment prevent or delay the progression of CKD into ESRD. Therefore, exploring pathogenesis essential for preventing treating CKD. There are variety trace elements in human body that interact each other within complex regulatory network. Iron copper both vital body. They critical maintaining bodily functions, dysregulation their metabolism cause many diseases, including disease. Ferroptosis new form cell death characterized by iron accumulation lipid peroxidation. Studies have shown ferroptosis closely related role abnormal its relationship remains unclear. Here, our current knowledge regarding metabolism, mechanism, diseases summarized. In addition, we discuss between explore possible provide potential therapeutic target

Язык: Английский

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MAMMALIAN COPPER HOMEOSTASIS: PHYSIOLOGIC ROLES AND MOLECULAR MECHANISMS

Physiological Reviews, Год журнала: 2024, Номер 105(1), С. 441 - 491

Опубликована: Авг. 22, 2024

In the past decade, evidence for numerous roles of copper (Cu) in mammalian physiology has grown exponentially. The discoveries Cu involvement cell signaling, autophagy, motility, differentiation, and regulated death (cuproptosis) have markedly extended list already known functions Cu, such as a cofactor essential metabolic enzymes, protein structural component, regulator trafficking. Novel unexpected transporting proteins enzymes been identified, new disorders homeostasis described. Significant progress made mechanistic studies two classic metabolism, Menkes disease Wilson’s disease, which paved way novel approaches to their treatment. discovery cuproptosis role metastatic growth increased interest targeting homeostatic pathways treat cancer. this review, we summarize established concepts field discuss how decade expand modify these concepts. brain metabolism functional speciation recently discovered attracted significant attention are highlighted review.

Язык: Английский

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Copper-instigated modulatory cell mortality mechanisms and progress in oncological treatment investigations

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Авг. 2, 2023

Copper, a transition metal, serves as an essential co-factor in numerous enzymatic active sites and constitutes vital trace element the human body, participating crucial life-sustaining activities such energy metabolism, antioxidation, coagulation, neurotransmitter synthesis, iron tetramer deposition. Maintaining equilibrium of copper ions within biological systems is paramount importance prevention atherosclerosis associated cardiovascular diseases. Copper induces cellular demise through diverse mechanisms, encompassing reactive oxygen species responses, apoptosis, necrosis, pyroptosis, mitochondrial dysfunction. Recent research has identified dubbed novel regulatory cell death modality—”cuprotosis”—wherein bind to acylated proteins tricarboxylic acid cycle respiration, resulting protein aggregation, subsequent downregulation iron-sulfur cluster expression, induction proteotoxic stress, eventual death. Scholars have synthesized complexes by combining with various ligands, exploring their significance applications cancer therapy. This review comprehensively examines multiple pathways copper-induced death, current status treatment.

Язык: Английский

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Copper homeostasis and cuproptosis in central nervous system diseases

Cell Death and Disease, Год журнала: 2024, Номер 15(11)

Опубликована: Ноя. 20, 2024

Abstract Copper (Cu), an indispensable micronutrient for the sustenance of living organisms, contributes significantly to a vast array fundamental metabolic processes. The human body maintains relatively low concentration copper, which is mostly found in bones, liver, and brain. Despite its concentration, Cu plays crucial role as element progression pathogenesis central nervous system (CNS) diseases. Extensive studies have been conducted recent years on copper homeostasis copper-induced cell death CNS disorders, including glioma, Alzheimer’s disease, Amyotrophic lateral sclerosis, Huntington’s stroke. Cuproptosis, novel pathway distinct from apoptosis, necrosis, pyroptosis, ferroptosis, has identified potentially intricately linked pathogenic mechanisms underlying various Therefore, systematic review cuproptosis their relationship with disorders could deepen our understanding these In addition, it may provide new insights strategies treatment disorders.

Язык: Английский

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The Cross-Communication of Cuproptosis and Regulated Cell Death in Human Pathophysiology

International Journal of Biological Sciences, Год журнала: 2023, Номер 20(1), С. 218 - 230

Опубликована: Ноя. 15, 2023

Copper (Cu) plays a crucial and diverse function in biological systems, acting as cofactor at numerous sites of enzymatic activity participating various physiological processes, including oxidative stress regulation, lipid metabolism, energy metabolism. Similar to other micronutrients, the body regulates Cu levels ensure homeostasis; any disruption homeostasis may result illnesses. Cuproptosis causes proteotoxic ultimately results cell death by binding ions lipid-acylated proteins during tricarboxylic acid cycle mitochondrial respiration. is not only involved regulatory (RCD), but also exogenous factors that induce cellular responses toxic outcomes. imbalances affect transmission several RCD messages. Therefore, this article presents thorough examination mechanisms Cu-induced well role complexes its pathophysiology.

Язык: Английский

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Cope with copper: From molecular mechanisms of cuproptosis to copper-related kidney diseases

International Immunopharmacology, Год журнала: 2024, Номер 133, С. 112075 - 112075

Опубликована: Апрель 24, 2024

Язык: Английский

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Inducers of Autophagy and Cell Death: Focus on Copper Metabolism

Ecotoxicology and Environmental Safety, Год журнала: 2025, Номер 290, С. 117725 - 117725

Опубликована: Янв. 1, 2025

Язык: Английский

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Copper(II) import and reduction are dependent on His-Met clusters in the extracellular amino terminus of human copper transporter-1

Journal of Biological Chemistry, Год журнала: 2022, Номер 298(3), С. 101631 - 101631

Опубликована: Янв. 26, 2022

Copper(I) is an essential metal for all life forms. Though Cu(II) the most abundant and stable state, its reduction to Cu(I) via unclear mechanism prerequisite bioutilization. In eukaryotes, copper transporter-1 (CTR1) primary high-affinity importer, although role in remain uncharacterized. Here we show that extracellular amino-terminus of human CTR1 contains two methionine-histidine clusters neighboring aspartates distinctly bind preceding import. We determined hCTR1 localizes at basolateral membrane polarized MDCK-II cells endocytosis Common-Recycling-Endosomes regulated by subsequent coordination methionine cluster. demonstrate transient binding both during process facilitated also act as another crucial determinant endocytosis. Mutating first Methionine cluster (7Met-Gly-Met9) Asp13 abrogated uptake upon treatment. This phenotype could be reverted treating with reduced nonreoxidizable Cu(I). histidine clusters, on other hand, are functioning limiting copper. Finally, N-terminal His-Met-Asp exhibit functional complementarity, second sufficient preserve copper-induced complete deletion propose a novel detailed which residues not only copper, but maintain intracellular uptake.

Язык: Английский

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