Copper metabolism in cell death and autophagy

Autophagy, Год журнала: 2023, Номер 19(8), С. 2175 - 2195

Опубликована: Апрель 14, 2023

Copper is an essential trace element in biological systems, maintaining the activity of enzymes and function transcription factors. However, at high concentrations, copper ions show increased toxicity by inducing regulated cell death, such as apoptosis, paraptosis, pyroptosis, ferroptosis, cuproptosis. Furthermore, can trigger macroautophagy/autophagy, a lysosome-dependent degradation pathway that plays dual role regulating survival or death fate cells under various stress conditions. Pathologically, impaired metabolism due to environmental genetic causes implicated variety human diseases, rare Wilson disease common cancers. Therapeutically, copper-based compounds are potential chemotherapeutic agents be used alone combination with other drugs approaches treat cancer. Here, we review progress made understanding metabolic processes their impact on regulation autophagy. This knowledge may help design future clinical tools improve cancer diagnosis treatment.

Язык: Английский

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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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Cuproptosis: p53-regulated metabolic cell death?

Cell Death and Differentiation, Год журнала: 2023, Номер 30(4), С. 876 - 884

Опубликована: Фев. 8, 2023

Abstract Cuproptosis is a novel type of copper-induced cell death that primarily occurs in cells utilize oxidative phosphorylation as the main metabolic pathway to produce energy. Copper directly associates with lipoylated proteins tricarboxylic acid cycle, leading disulfide-bond-dependent aggregation these proteins, destabilization iron-sulfur cluster and consequent proteotoxic stress. Cancer prefer glycolysis (Warburg effect) for producing intermediate metabolites energy, thereby achieving resistance cuproptosis. Interestingly, tumor suppressor p53 crucial regulator inhibits drives switch towards cancer cells. Additionally, regulates biogenesis clusters copper chelator glutathione, which are two critical components cuproptotic pathway, suggesting this might play role Furthermore, possible roles mutant regulating cuproptosis discussed. In essay, we review recent progress understanding mechanism underlying cuproptosis, revisit regulation glutathione biosynthesis, propose several potential mechanisms wild-type p53-mediated regulation.

Язык: Английский

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Cuproptosis: A novel therapeutic target for overcoming cancer drug resistance

Drug Resistance Updates, Год журнала: 2023, Номер 72, С. 101018 - 101018

Опубликована: Ноя. 11, 2023

Cuproptosis is a newly identified form of cell death driven by copper. Recently, the role copper and triggered in pathogenesis cancers have attracted attentions. has garnered enormous interest cancer research communities because its great potential for therapy. Copper-based treatment exerts an inhibiting tumor growth may open door chemotherapy-insensitive tumors. In this review, we provide critical analysis on homeostasis dysregulation development progression cancers. Then core molecular mechanisms cuproptosis discussed, followed summarizing current understanding copper-based agents (copper chelators, ionophores, complexes-based dynamic therapy) treatment. Additionally, summarize emerging data ionophores to subdue chemotherapy resistance different types We also review small-molecule compounds nanoparticles (NPs) that kill cells inducing cuproptosis, which will shed new light anticancer drugs through future. Finally, important concepts pressing questions future should be focused were discussed. This article suggests targeting could novel antitumor therapy strategy overcome drug resistance.

Язык: Английский

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Prognostic analysis of cuproptosis-related gene in triple-negative breast cancer

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Авг. 1, 2022

Cuproptosis is a copper-dependent cell death mechanism that associated with tumor progression, prognosis, and immune response. However, the potential role of cuproptosis-related genes (CRGs) in microenvironment (TME) triple-negative breast cancer (TNBC) remains unclear.In total, 346 TNBC samples were collected from The Cancer Genome Atlas database three Gene Expression Omnibus datasets, classified using R software packages. relationships between different subgroups clinical pathological characteristics, infiltration mutation status TME examined. Finally, nomogram calibration curve constructed to predict patient survival probability improve applicability CRG_score.We identified two CRG clusters characteristics highly consistent those immune-inflamed immune-desert clusters. Furthermore, we demonstrated gene signature can be used evaluate infiltration, features, prognostic status. Low CRG_scores characterized by high burden activation, good probability, more immunoreactivity CTLA4, while activation stromal pathways immunosuppression.This study revealed effects CRGs on TME, clinicopathological prognosis TNBC. closely immunity are tool for predicting prognosis. Our data provide new directions development novel drugs future.

Язык: Английский

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Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 14, 2024

Iron, an essential mineral in the body, is involved numerous physiological processes, making maintenance of iron homeostasis crucial for overall health. Both overload and deficiency can cause various disorders human diseases. Ferroptosis, a form cell death dependent on iron, characterized by extensive peroxidation lipids. Unlike other kinds classical unprogrammed death, ferroptosis primarily linked to disruptions metabolism, lipid peroxidation, antioxidant system imbalance. Ferroptosis regulated through transcription, translation, post-translational modifications, which affect cellular sensitivity ferroptosis. Over past decade or so, diseases have been as part their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous cardiovascular musculoskeletal Ferroptosis-related proteins become attractive targets many major that are currently incurable, some regulators shown therapeutic effects clinical trials although further validation potential needed. Therefore, in-depth analysis its molecular mechanisms may offer additional strategies prevention treatment. In this review, we discuss significance contribution etiology development along with evidence supporting targeting approach. Importantly, evaluate recent promising interventions, providing guidance future targeted treatment therapies against

Язык: Английский

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Regulatory roles of copper metabolism and cuproptosis in human cancers

Frontiers in Oncology, Год журнала: 2023, Номер 13

Опубликована: Март 23, 2023

Copper is an essential micronutrient for human body and plays a vital role in various biological processes including cellular respiration free radical detoxification. Generally, copper metabolism the stable state, there are specific mechanisms to regulate maintain homeostasis. Dysregulation of may have great connection with types diseases, such as Wilson disease causing overload Menkes deficiency. Cancer presents high mortality rates world due unlimited proliferation potential, apoptosis escape immune properties induce organ failure. thought cancer, elevated levels cancer tissue serum. also affects tumor progression by affecting angiogenesis, metastasis other processes. Notably, cuproptosis novel form cell death that provide targeting strategies developing therapy. chelators ionophores two coordinating compounds treatment cancer. This review will explore relationship between cancers, clarify targeted

Язык: Английский

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Identification of copper metabolism-related subtypes and establishment of the prognostic model in ovarian cancer

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Март 6, 2023

Ovarian cancer (OC) is one of the most common and malignant gynecological malignancies in gynecology. On other hand, dysregulation copper metabolism (CM) closely associated with tumourigenesis progression. Here, we investigated impact genes (CMRGs) on prognosis OC, discovered various CM clusters, built a risk model to evaluate patient prognosis, immunological features, therapy response.15 CMRGs affecting OC patients were identified The Cancer Genome Atlas (TCGA). Consensus Clustering was used identify two clusters. lasso-cox methods establish metabolism-related gene prognostic signature (CMRGPS) based differentially expressed GSE63885 cohort as an external validation cohort. Expression score-associated verified by single-cell sequencing quantitative real-time PCR (qRT-PCR). Nomograms visually depict clinical value CMRGPS. Differences traits, immune cell infiltration, tumor mutational load (TMB) between groups also extensively examined. Tumour Immune Dysfunction Rejection (TIDE) Phenotype Score (IPS) validate whether CMRGPS could predict response immunotherapy patients.In TCGA cohorts, clusters that differed significantly terms overall survival (OS) microenvironment. We then created containing 11 confirmed its reliable predictive power for patients. expression score-related validated qRT-PCR. Patients divided into low-risk (LR) high-risk (HR) median score, better LR group. 5-year AUC reached 0.74. Enrichment analysis showed group immune-related pathways. results TIDE IPS group.Our study, therefore, provides valuable tool further guide management tailor treatment offering new insights individualized treatment.

Язык: Английский

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Gold Nanoparticles as Exquisite Colorimetric Transducers for Water Pollutant Detection

ACS Applied Materials & Interfaces, Год журнала: 2023, Номер 15(16), С. 19785 - 19806

Опубликована: Апрель 17, 2023

Gold nanoparticles (AuNPs) are useful nanomaterials as transducers for colorimetric sensors because of their high extinction coefficient and ability to change color depending on aggregation status. Therefore, over the past few decades, AuNP-based have been widely applied in several environmental biological applications, including detection water pollutants. According various studies, pollutants classified into heavy metals or cationic metal ions, toxins, pesticides. Notably, many researchers interested AuNP that detect with sensitivity selectivity, while offering no adverse issues terms use. This review provides a representative overview detecting In particular, we emphasize advantages pollutant low toxicity, stability, facile processability, unique optical properties. Next, discuss status quo future prospects We believe this will promote research development next-generation detection.

Язык: Английский

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The crosstalk between copper-induced oxidative stress and cuproptosis: a novel potential anticancer paradigm

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Июль 5, 2024

Abstract Copper is a crucial trace element that plays role in various pathophysiological processes the human body. also acts as transition metal involved redox reactions, contributing to generation of reactive oxygen species (ROS). Under prolonged and increased ROS levels, oxidative stress occurs, which has been implicated different types regulated cell death. The recent discovery cuproptosis, copper-dependent death pathway distinct from other known forms, raised interest researchers field cancer therapy. Herein, present work aims outline current understanding with an emphasis on its anticancer activities through interplay copper-induced stress, thereby providing new ideas for therapeutic approaches targeting modes future.

Язык: Английский

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