Copper homeostasis and copper-induced cell death： Novel targeting for intervention in the pathogenesis of vascular aging DOI Open Access
Zhuoying Chen, Yuanyuan Li, Xiangjie Liu

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 169, P. 115839 - 115839

Published: Nov. 16, 2023

Copper-induced cell death, also known as cuproptosis, is distinct from other types of death such apoptosis, necrosis, and ferroptosis. It can trigger the accumulation lethal reactive oxygen species, leading to onset progression aging. The significant increases in copper ion levels aging populations confirm a close relationship between homeostasis vascular On hand, closely related occurrence various cardiovascular diseases throughout process. However, specific causes are not clear, different living environments stress patterns lead individualized By exploring correlations copper-induced aging, we gain novel perspective on pathogenesis enhance prognosis atherosclerosis. This article aims provide comprehensive review impacts including their effects endothelial cells, smooth muscle oxidative stress, ferroptosis, intestinal flora, factors. Furthermore, intend discuss potential strategies involving cuproptosis new insights for copper-related

Language: Английский

Copper-dependent autophagic degradation of GPX4 drives ferroptosis DOI Creative Commons
Qian‐Li Xue, Yan Ding, Xi Chen

et al.

Autophagy, Journal Year: 2023, Volume and Issue: 19(7), P. 1982 - 1996

Published: Jan. 9, 2023

Ferroptosis is a type of iron-dependent regulated cell death characterized by unrestricted lipid peroxidation and membrane damage. Although GPX4 (glutathione peroxidase 4) plays master role in blocking ferroptosis eliminating phospholipid hydroperoxides, the regulation remains poorly understood. Here, we report an unexpected for copper promoting ferroptotic death, but not cuproptosis, inducing macroautophagic/autophagic degradation GPX4. Copper chelators reduce sensitivity do inhibit other types such as apoptosis, necroptosis, alkaliptosis. Conversely, exogenous increases ubiquitination formation aggregates directly binding to protein cysteines C107 C148. TAX1BP1 (Tax1 1) then acts autophagic receptor subsequent response stress. Consequently, enhances ferroptosis-mediated tumor suppression mouse model pancreatic cancer tumor, whereas attenuate experimental acute pancreatitis associated with ferroptosis. Taken together, these findings provide new insights into link between metal stress autophagy-dependent death.Abbreviations: CALCOCO2, calcium coiled-coil domain 2; GPX4, glutathione 4; MAP1LC3A/B, microtubule 1 light chain 3 alpha/beta; MPO, myeloperoxidase; NCOA4, nuclear coactivator OPTN, optineurin; PDAC, ductal adenocarcinoma; RIPK1, interacting serine/threonine kinase 1; ROS, reactive oxygen species; SLC40A1, solute carrier family 40 member SQSTM1, sequestosome TAX1BP1, Tax1 TEPA, tetraethylenepentamine; TM, tetrathiomolybdate.

Language: Английский

Citations

312
Cuproptosis scoring system to predict the clinical outcome and immune response in bladder cancer DOI Creative Commons
Qiang Song, Rui Zhou, Fangpeng Shu

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 4, 2022

Cuproptosis is a novel copper ion-dependent cell death type being regulated in cells, and this quite different from the common patterns such as apoptosis, pyroptosis, necroptosis, ferroptosis. Interestingly, like with patterns, cuproptosis-related genes have recently been reported to regulate occurrence progression of various tumors. However, bladder cancer, link between cuproptosis clinical outcome, tumor microenvironment (TME) modification, immunotherapy unknown. To determine role cuprotosis microenvironment, we systematically examined characteristic 10 cancer (BLCA). By analyzing principal component data, established score degree among patients. Finally, evaluated potential these values predicting BLCA prognosis treatment responses. A comprehensive study mutations specimens was conducted at genetic level, their expression survival were using The Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO). Two constructed based on transcription level genes, featuring differences infiltrating landscape immune cells (especially T dendritic cells) interactions TME. Our further demonstrated that may predict prognosis, immunophenotype sensitivity chemotherapy, response development are likely be influenced by cuproptosis, which involve diverse complex pattern our enhance understanding infiltrations guide more potent interventions.

Language: Английский

Citations

117
Prognostic analysis of cuproptosis-related gene in triple-negative breast cancer DOI Creative Commons

Shengnan Sha,

Luyi Si,

Xinrui Wu

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 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.

Language: Английский

Citations

101
Cuproptosis-related lncRNA predict prognosis and immune response of lung adenocarcinoma DOI Creative Commons
Fangwei Wang, Hongsheng Lin, Qisheng Su

et al.

World Journal of Surgical Oncology, Journal Year: 2022, Volume and Issue: 20(1)

Published: Sept. 1, 2022

Lung adenocarcinoma (LUAD) accounts for 50% of lung cancers, with high mortality and poor prognosis. Long non-coding RNA (lncRNA) plays a vital role in the progression tumors. Cuproptosis is newly discovered form cell death that highly investigated. Therefore, present study, we aimed to investigate cuproptosis-related lncRNA signature clinical prognosis prediction immunotherapy relationship drug sensitivity.Genomic data were obtained from The Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) databases, genes studies. prognostic was constructed by co-expression analysis Cox regression analysis. Patients divided into low risk groups, then, further series model validations carried out assess value signature. Subsequently, lncRNAs analyzed gene ontology (GO), Kyoto Encyclopedia Genes Genomes Enrichment (KEGG), immune-related functions, tumor mutation burden (TMB). Finally, used immune dysfunction exclusion (TIDE) algorithms on escape lncRNAs, thereby identifying its sensitivity toward potential drugs LUAD.A total 16 obtained, developed. We found high-risk patients had worse overall survival (OS) progression-free (PFS) higher mortality. Independent analyses, ROC, C-index, nomogram showed can accurately predict patients. heatmap distinct distribution high- low-risk lncRNAs. biological functions are associated development. also such as antiviral activity, suppressed who mutations oncogenes. OS poorer TMB. TIDE have greater less effective immunotherapy.To conclude, LUAD may provide new insights applications immunotherapy.

Language: Английский

Citations

83
Cope with copper: From copper linked mechanisms to copper-based clinical cancer therapies DOI
Xidi Wang, Miao Zhou, Yu Liu

et al.

Cancer Letters, Journal Year: 2023, Volume and Issue: 561, P. 216157 - 216157

Published: April 1, 2023

Language: Английский

Citations

77
Copper in cancer: from limiting nutrient to therapeutic target DOI Creative Commons
Xiaolong Tang,

Zaihua Yan,

Yandong Miao

et al.

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: June 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.

Language: Английский

Citations

57
Copper homeostasis and cuproptosis in mitochondria DOI

Ziying Tian,

Su Jiang,

Jieyu Zhou

et al.

Life Sciences, Journal Year: 2023, Volume and Issue: 334, P. 122223 - 122223

Published: Oct. 29, 2023

Language: Английский

Citations

42
Sleep fragmentation exacerbates myocardial ischemia‒reperfusion injury by promoting copper overload in cardiomyocytes DOI Creative Commons
Na Chen, Lizhe Guo, Lu Wang

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 7, 2024

Abstract Sleep disorders increase the risk and mortality of heart disease, but brain-heart interaction has not yet been fully elucidated. Cuproptosis is a copper-dependent type cell death activated by excessive accumulation intracellular copper. Here, we showed that 16 weeks sleep fragmentation (SF) resulted in elevated copper levels male mouse exacerbated myocardial ischemia–reperfusion injury with increased cuproptosis apoptosis. Mechanistically, found SF promotes sympathetic overactivity, increases germination nerve terminals, level norepinephrine cardiac tissue, thereby inhibits VPS35 expression leads to impaired ATP7A related transport overload cardiomyocytes. Copper further apoptosis, these effects can be rescued excision or administration chelating agent. Our study elucidates one molecular mechanisms which aggravate suggests possible targets for intervention.

Language: Английский

Citations

22
Copper in colorectal cancer: From copper‐related mechanisms to clinical cancer therapies DOI Creative Commons
Yuhong Wang, Pei Pei, Kai Yang

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(6)

Published: May 28, 2024

Abstract Copper, a trace element and vital cofactor, plays crucial role in the maintenance of biological functions. Recent evidence has established significant correlations between copper levels, cancer development metastasis. The strong redox‐active properties offer both benefits disadvantages to cells. intestinal tract, which is primarily responsible for uptake regulation, may suffer from an imbalance homeostasis. Colorectal (CRC) most prevalent primary tract aggressive malignant disease with limited therapeutic options. Current research focused on relationship CRC. Innovative concepts, such as cuproplasia cuproptosis, are being explored understand copper‐related cellular proliferation death. Cuproplasia regulation cell that mediated by enzymatic nonenzymatic copper‐modulated activities. Whereas, cuproptosis refers death induced excess via promoting abnormal oligomerisation lipoylated proteins within tricarboxylic acid cycle, well diminishing levels iron‐sulphur cluster proteins. A comprehensive understanding mechanisms offers new avenues CRC treatment. In this review, we summarise evolving molecular mechanisms, ranging intracellular concentrations discovered, discuss pathogenesis, progression potential therapies Understanding will help provide theoretical foundation innovative treatment strategies management.

Language: Английский

Citations

20
Redox homeostasis in cardiac fibrosis: Focus on metal ion metabolism DOI Creative Commons
Zhenyu Liu,

Zhiyan Liu,

Li-Chan Lin

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 71, P. 103109 - 103109

Published: March 1, 2024

Cardiac fibrosis is a major public health problem worldwide, with high morbidity and mortality, affecting almost all patients heart disease worldwide. It characterized by fibroblast activation, abnormal proliferation, excessive deposition, distribution of extracellular matrix (ECM) proteins. The maladaptive process cardiac complex often involves multiple mechanisms. With the increasing research on fibrosis, redox has been recognized as an important part remodeling, imbalance in homeostasis can adversely affect function structure heart. metabolism metal ions essential for life, cells impair variety biochemical processes, especially redox. However, current ion still very limited. This review comprehensively examines effects (iron, copper, calcium, zinc) metabolism-mediated outlines possible therapeutic interventions, addresses ongoing challenges this rapidly evolving field.

Language: Английский

Citations

16