The molecular mechanisms of cuproptosis and its relevance to cardiovascular disease

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 163, P. 114830 - 114830

Published: May 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.

Language: Английский

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Copper homeostasis and cuproptosis in cardiovascular disease therapeutics

Trends in Pharmacological Sciences, Journal Year: 2023, Volume and Issue: 44(9), P. 573 - 585

Published: July 25, 2023

Language: 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, Journal Year: 2024, Volume and Issue: 25(2), P. 824 - 824

Published: Jan. 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.

Language: 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, Journal Year: 2024, Volume and Issue: 56, P. 102223 - 102223

Published: March 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.

Language: Английский

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

Cancers, Journal Year: 2024, Volume and Issue: 16(3), P. 647 - 647

Published: Feb. 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.

Language: Английский

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Copper Homeostasis in Chronic Kidney Disease and Its Crosstalk with Ferroptosis

Pharmacological Research, Journal Year: 2024, Volume and Issue: 202, P. 107139 - 107139

Published: March 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

Language: Английский

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Targeting cuproptosis for cancer therapy: mechanistic insights and clinical perspectives

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Aug. 16, 2024

Cuproptosis is a newly identified form of cell death induced by excessive copper (Cu) accumulation within cells. Mechanistically, cuproptosis results from Cu-induced aggregation dihydrolipoamide S-acetyltransferase, correlated with the mitochondrial tricarboxylic acid cycle and loss iron–sulfur cluster proteins, ultimately resulting in proteotoxic stress triggering death. Recently, has garnered significant interest tumor research due to its potential as crucial therapeutic strategy against cancer. In this review, we summarized cellular molecular mechanisms relationship other types Additionally, reviewed current drugs or strategies available induce cells, including Cu ionophores, small compounds, nanomedicine. Furthermore, targeted metabolism specific regulatory genes cancer therapy enhance sensitivity cuproptosis. Finally, discussed feasibility targeting overcome chemotherapy immunotherapy resistance suggested future directions. This study that could open new avenues for developing therapy.

Language: 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, Journal Year: 2024, Volume and Issue: 18(12), P. 9100 - 9113

Published: March 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.

Language: Английский

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Copper-instigated modulatory cell mortality mechanisms and progress in kidney diseases

Renal Failure, Journal Year: 2025, Volume and Issue: 47(1)

Published: Jan. 13, 2025

Copper is a vital cofactor in various enzymes, plays pivotal role maintaining cell homeostasis. When copper metabolism disordered and mitochondrial dysfunction impaired, programmed death such as apoptosis, paraptosis, pyroptosis, ferroptosis, cuproptosis, autophagy necroptosis can be induced. In this review, we focus on the metabolic mechanisms of copper. addition, discuss mechanism by which induces deaths. Finally, review examines copper's involvement prevalent kidney diseases acute injury chronic disease. The findings indicate that use chelators or plant extracts mitigate damage reducing accumulation, offering novel insights into pathogenesis treatment strategies for diseases.

Language: Английский

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Role of cuproptosis in understanding diseases

Human Cell, Journal Year: 2023, Volume and Issue: 36(4), P. 1244 - 1252

Published: May 8, 2023

Language: Английский

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