Cuproptosis: Mechanism, role, and advances in urological malignancies

Medicinal Research Reviews, Год журнала: 2024, Номер 44(4), С. 1662 - 1682

Опубликована: Фев. 1, 2024

Prostate, bladder, and kidney cancers are the most common malignancies of urinary system. Chemotherapeutic drugs generally used as adjuvant treatment in middle, late, or recurrence stages after surgery for urologic cancers. However, traditional chemotherapy is plagued by problems such poor efficacy, severe side effects, complications. Copper-containing nanomedicines promising novel cancer modalities that can potentially overcome these disadvantages. Copper homeostasis cuproptosis play crucial roles development, adaptability, therapeutic sensitivity urological malignancies. Cuproptosis refers to direct binding copper ions lipoylated components tricarboxylic acid cycle, leading protein oligomerization, loss iron-sulfur proteins, proteotoxic stress, cell death. This review focuses on well recent findings Furthermore, we highlight potential applications copper- cuproptosis-targeted therapies better understand cuproptosis-based tumors future.

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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Chemiluminescent transition metal complexes: Mechanisms and applications

Coordination Chemistry Reviews, Год журнала: 2025, Номер 530, С. 216495 - 216495

Опубликована: Фев. 5, 2025

Язык: Английский

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Bridging the gap between theory and treatment: Transition metal complexes as successful candidates in medicine

Coordination Chemistry Reviews, Год журнала: 2025, Номер 531, С. 216477 - 216477

Опубликована: Фев. 8, 2025

Язык: Английский

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Human cells experience a Zn2+ pulse in early G1

Cell Reports, Год журнала: 2023, Номер 42(6), С. 112656 - 112656

Опубликована: Июнь 1, 2023

Zinc is an essential micronutrient required for all domains of life. Cells maintain zinc homeostasis using a network transporters, buffers, and transcription factors. mammalian cell proliferation, remodeled during the cycle, but whether labile changes in naturally cycling cells has not been established. We use genetically encoded fluorescent reporters, long-term time-lapse imaging, computational tools to track over cycle response growth media knockdown zinc-regulatory factor MTF-1. experience pulse early G1, whose magnitude varies with media. Knockdown MTF-1 increases pulse. Our results suggest that need minimum proliferate if levels are too high, pause proliferation until cellular lowered.

Язык: Английский

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α-lipoic acid ameliorates consequences of copper overload by up-regulating selenoproteins and decreasing redox misbalance

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(40)

Опубликована: Сен. 26, 2023

α-lipoic acid (LA) is an essential cofactor for mitochondrial dehydrogenases and required cell growth, metabolic fuel production, antioxidant defense. In vitro, LA binds copper (Cu) with high affinity as endogenous membrane permeable metabolite could be advantageous in mitigating the consequences of Cu overload human diseases. We tested this hypothesis 3T3-L1 preadipocytes inactivated transporter Atp7a; these cells accumulate show morphologic changes mitochondria impairment. Treatment corrected morphology Atp7a −/− similar to chelator bathocuproinedisulfonate (BCS) improved function; however, mechanisms BCS action were different. Unlike BCS, did not decrease intracellular but instead increased selenium levels that low cells. Proteome analysis confirmed distinct responses compounds identified upregulation selenoproteins major effect on preadipocytes. Upregulation was associated GSH:GSSG ratio cellular compartments, which lowered by elevated Cu, reversal protein oxidation. Thus, diminishes toxic effects improving redox environment. also are decreased tissues a Wilson disease animal model, especially liver, making attractive candidate supplemental treatment disease.

Язык: Английский

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Structural Role of Cadmium and Zinc in Metallothionein Oxidation by Hydrogen Peroxide: The Resilience of Metal–Thiolate Clusters

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(11), С. 6383 - 6397

Опубликована: Март 13, 2023

Oxidative stress is a state involving an imbalance of reactive oxygen species in cell and linked to variety diseases. The metal-binding protein metallothionein (MT) may play role protection due its high cysteine content. Many studies have shown that oxidative will cause MT both form disulfide bonds release bound metals. However, on the more biologically relevant partially metalated MTs been largely neglected. Additionally, most date used spectroscopic methods cannot detect specific intermediate species. In this paper, we describe oxidation subsequent metal displacement pathway fully with hydrogen peroxide. rates reactions were monitored using electrospray ionization mass spectrometry (ESI-MS) techniques, which resolved characterized individual Mx(SH)yMT rate constants calculated for each formation. Through ESI-MS circular dichroism spectroscopy, it was found three metals β-domain first be released from MTs. Cd(II) Cd(II)-bound rearranged protective Cd4MT cluster structure upon exposure oxidation. Zn(II)-bound oxidized at faster as Zn(II) did not rearrange response density functional theory calculations showed terminally cysteines negative thus susceptible than bridging cysteines. results study highlight importance metal-thiolate structures identity MT's

Язык: Английский

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The structural characteristics of Crassostrea gigas peptide-zinc complexes and the bioactive mechanism of their enhanced zinc absorption

Food Bioscience, Год журнала: 2024, Номер 58, С. 103722 - 103722

Опубликована: Фев. 6, 2024

Язык: Английский

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Metals and metallothionein evolution in snails: a contribution to the concept of metal-specific functionality from an animal model group

BioMetals, Год журнала: 2024, Номер 37(3), С. 671 - 696

Опубликована: Фев. 28, 2024

This is a critical review of what we know so far about the evolution metallothioneins (MTs) in Gastropoda (snails, whelks, limpets and slugs), an important class molluscs with over 90,000 known species. Particular attention will be paid to snail MTs relation role some metallic trace elements (cadmium, zinc copper) their interaction MTs, also compared from other animal phyla. The article highlights distinction, yet close relationship, between structural metal-selective binding properties gastropod physiological functionality living organism. It appears that course Gastropoda, metal cadmium (Cd) must have played essential development Cd-selective MT variants. shown how structures basal clades evolved by testing optimizing different combinations ancestral novel domains, these domains become established modern recent clades. In this context, question adaptation new habitats lifestyles has affected original traits lineages addressed. 3D preferences highlighted exemplarily littorinid helicid snails. Finally, importance requirements pathways tissues cells for shaping respective isoforms shown.

Язык: Английский

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Fe-S clusters masquerading as zinc finger proteins

Journal of Inorganic Biochemistry, Год журнала: 2022, Номер 230, С. 111756 - 111756

Опубликована: Фев. 10, 2022

Язык: Английский

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