The molecular mechanisms of cuproptosis and its relevance to cardiovascular disease

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 163, С. 114830 - 114830

Опубликована: Май 8, 2023

Recently, cuproptosis has been demonstrated to be a new non-apototic cell death mode that is characterized by copper dependence and the regulation of mitochondrial respiration. Cuproptosis distinct from known modes such as apoptosis, necrosis, pyroptosis, or ferroptosis. Excessive induces promoting protein toxic stress reactions via copper-dependent anomalous oligomerization lipoylation proteins in tricarboxylic acid (TCA) cycle reducing iron-sulfur cluster levels. Ferredoxin1 (FDX1) promotes dihydrolipoyl transacetylase (DLAT) lipoacylation abates Cu2+ Cu+, inducing death. Copper homeostasis depends on transporter, disturbances this cause cuproptosis. Recent evidence shown plays significant role occurrence development many cardiovascular diseases, myocardial ischemia/reperfusion (I/R) injury, heart failure, atherosclerosis, arrhythmias. chelators, ammonium tetrathiomolybdate(VI) DL-Penicillamine, may ease above diseases inhibiting pathway. Oxidative phosphorylation inhibitors inhibit response. In conclusion, an essential disease pathogenesis. Inhibition expected become potential treatment. Here, we will thoroughly review molecular mechanisms involved its significance disease.

Язык: Английский

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Copper homeostasis and cuproptosis in cardiovascular disease therapeutics

Trends in Pharmacological Sciences, Год журнала: 2023, Номер 44(9), С. 573 - 585

Опубликована: Июль 25, 2023

Язык: Английский

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The Dual Roles of Activating Transcription Factor 3 (ATF3) in Inflammation, Apoptosis, Ferroptosis, and Pathogen Infection Responses

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(2), С. 824 - 824

Опубликована: Янв. 9, 2024

Transcription factors are pivotal regulators in the cellular life process. Activating transcription factor 3 (ATF3), a member of ATF/CREB (cAMP response element-binding protein) family, plays crucial role as cells respond to various stresses and damage. As factor, ATF3 significantly influences signal transduction regulation, orchestrating variety signaling pathways, including apoptosis, ferroptosis, differentiation. In addition, serves an essential link between inflammation, oxidative stress, immune responses. This review summarizes recent advances research on activation its regulating inflammatory responses, cell ferroptosis while exploring dual functions these processes. Additionally, this article discusses diseases related pathogenic microbial infections. Our may be helpful better understand responses disease progression, thus promoting advancements clinical treatments for inflammation stress-related diseases.

Язык: Английский

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Cuproptosis: Unraveling the Mechanisms of Copper-Induced Cell Death and Its Implication in Cancer Therapy

Cancers, Год журнала: 2024, Номер 16(3), С. 647 - 647

Опубликована: Фев. 2, 2024

Copper, an essential element for various biological processes, demands precise regulation to avert detrimental health effects and potential cell toxicity. This paper explores the mechanisms of copper-induced death, known as cuproptosis, its disease implications, including cancer therapy. Copper ionophores, such elesclomol disulfiram, increase intracellular copper levels. elevation triggers oxidative stress subsequent offering implications in Additionally, ionophores disrupt mitochondrial respiration protein lipoylation, further contributing toxicity death. Potential targets biomarkers are identified, can be targeted those proteins trigger cuproptosis. The role different cancers is discussed understand therapies using nanomaterials, chelators. Furthermore, explored through diseases Wilson Menkes physiological copper. Exploring cuproptosis presents opportunity improve treatments copper-related disorders cancers, with bring significant advancements modern medicine.

Язык: Английский

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Cuprous oxide nanocomposites with photothermal (PTT) and chemical dynamics (CDT) effects induce cuproptosis in breast cancer using the strategy of increasing inflow and reducing outflow

Nano Today, Год журнала: 2024, Номер 56, С. 102223 - 102223

Опубликована: Март 8, 2024

Chemotherapy is a crucial adjuvant method of treating breast cancer, but it fails to achieve preferable prognosis as the malignant cells eventually develop drug-resistance. Reduced chemotherapeutic sensitivity primarily caused by endogenous and exogenous resistance during treatment. Cuproptosis newly discovered immunogenic cell death (ICD), characterized accumulation copper (Cu) ions inside tumor cells. However, intracellular Cu ion concentrations can hardly reach desired levels induce cuproptosis due limited import via existing ionophores synchronous export ATP-Cu pump. Herein, our research developed an elesclomol (ES) loaded cuprous oxide (Cu2O) nanocomposite, called PEG@Cu2O-ES, solve this dilemma. Our designed PEG@Cu2O-ES could efficiently enter cancer cells, release encapsulated ES Cu2O, while photothermal (PTT) effect Cu2O induced near-infrared II region (NIR-II) radiation in turn accelerate releasing process. discharged substantial amounts cytoplasm, which directly engaged tricarboxylic acid (TCA) cycle mitochondria, resulting some extent. As result PTT-enhanced Fenton-like reactions, generated quantity reactive oxygen species (ROS) that attacked pump on cells' membranes, thereby reducing outflow aggravating cuproptosis. Additionally, free further promoted from microenvironment (TME) exacerbated with higher efficiency. In vivo, nanocomposites showed strong anti-tumor inducing cuproptosis, well ability reprogram TME increase response-sensitivity programmed protein-1 antibody (αPD-1). conclusion, study provides promising strategy combining nano-drug αPD-1 for sensitizing immunotherapy chemotherapy-resistant cancer.

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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Role of cuproptosis in understanding diseases

Human Cell, Год журнала: 2023, Номер 36(4), С. 1244 - 1252

Опубликована: Май 8, 2023

Язык: Английский

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Copper and Zinc Particles as Regulators of Cardiovascular System Function—A Review

Nutrients, Год журнала: 2023, Номер 15(13), С. 3040 - 3040

Опубликована: Июль 5, 2023

Copper and zinc are micronutrients that play a crucial role in many cellular pathways, act as cofactors enzymatic systems, hence, modulate enzyme activity. The regulation of these elements homeostasis is precisely controlled by various mechanisms. Superoxide dismutase (SOD) an requiring both copper for proper functioning. Additionally, there interaction between the concentrations zinc. Dietary ingestion large amounts augments intestinal absorption this trace element, resulting deficiency secondary to excess. presence overabundance has detrimental impact on cardiovascular system; however, vascular contractility varies. plays modulation remodeling cardiac tissue, phenomenon cuproptosis been linked pathogenesis coronary artery disease. observable effect vasorelaxation mediated nitric oxide. maintenance levels within organism influences SOD essential myocardial ischemia/reperfusion injury. Recently, effects metal nanoparticles have investigated due their unique characteristics. On other hand, dietary introduction may result dysfunction, oxidative stress, DNA damage. intake affect function, but more research needed.

Язык: Английский

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Coordination Self-Assembled AuTPyP-Cu Metal–Organic Framework Nanosheets with pH/Ultrasound Dual-Responsiveness for Synergistically Triggering Cuproptosis-Augmented Chemotherapy

ACS Nano, Год журнала: 2024, Номер 18(12), С. 9100 - 9113

Опубликована: Март 13, 2024

Reactive oxygen species (ROS) mediated tumor cell death is a powerful anticancer strategy. Cuproptosis copper-dependent and ROS-mediated prospective therapy However, the complex microenvironment (TME), low specificity, poor efficiency, lack of imaging capability impair output current cuproptosis drugs. Herein, we designed dual-responsive two-dimensional metal–organic framework (2D MOF) nanotheranostic via coordination self-assembly strategy using Au(III) tetra-(4-pyridyl) porphine (AuTPyP) as ligand copper ions (Cu2+) nodes. The dual-stimulus combined with protonation pyridyl group in AuTPyP deep-penetration ultrasound (US) together triggered controlled release an acidic TME. ultrathin structure (3.0 nm) nanotheranostics promoted process. released Cu2+ was reduced to Cu+ by depleting overexpressed glutathione (GSH) tumor, which not only activated Ferredoxin 1 (FDX1)-mediated but also catalyzed hydrogen peroxide (H2O2) into reactive Fenton-like reaction. Simultaneously, could specifically bind thioredoxin reductase activate redox imbalance cells. These selectively induced significant mitochondrial vacuoles prominent did damage normal fluorescence magnetic resonance (MRI) results verified this target HeLa greatly promote self-enhanced effect chemotherapy/cuproptosis inhibition efficiency. work helped elucidate assembly multiresponsive high-specificity ROS regulation for application therapy.

Язык: Английский

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Comprehensive bioinformatics analysis reveals the role of cuproptosis-related gene Ube2d3 in myocardial infarction

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Фев. 19, 2024

Background Myocardial infarction (MI) caused by severe coronary artery disease has high incidence and mortality rates, making its prevention treatment a central challenging aspect of clinical work for cardiovascular practitioners. Recently, researchers have turned their attention to novel mechanism cell death Cu 2+ , cuproptosis. Methods This study integrated data from three MI-related bulk datasets downloaded the Gene Expression Omnibus (GEO) database, identified 16 differentially expressed genes (DEGs) related cuproptosis taking intersection 6378 DEGs obtained differential analysis with 49 cuproptosis-related genes. Four hub genes, Dbt, Dlat, Ube2d1 Ube2d3, were screened out through random forest Lasso analysis. In group, showed low expression, while Ube2d3 exhibited expression. Results Focusing on subsequent functional studies, we confirmed expression in MI group qRT-PCR Western Blot detection after successful construction mouse model left anterior descending (LAD) ligation, further clarified correlation development detecting levels proteins. Moreover, vitro experiments, was be highly oxygen-glucose deprivation (OGD)-treated cardiomyocytes AC16. order clarify role knocked down OGD-treated AC16 cells, Ube2d3’s promoting hypoxia damage cells inducing cuproptosis, as evidenced MTT, TUNEL, LDH release Conclusion summary, our findings indicate that regulates affect progression MI.

Язык: Английский

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