Pore-forming proteins as drivers of membrane permeabilization in cell death pathways

Nature Reviews Molecular Cell Biology, Год журнала: 2022, Номер 24(5), С. 312 - 333

Опубликована: Дек. 21, 2022

Язык: Английский

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TNFα modulates PANX1 activation to promote ATP release and enhance P2RX7-mediated antitumor immune responses after chemotherapy in colorectal cancer

Cell Death and Disease, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 9, 2024

ATP and its receptor P2RX7 exert a pivotal effect on antitumor immunity during chemotherapy-induced immunogenic cell death (ICD). Here, we demonstrated that TNFα-mediated PANX1 cleavage was essential for release in response to chemotherapy colorectal cancer (CRC). TNFα promoted via caspase 8/3-dependent pathway enhance immunogenicity, leading dendritic maturation T-cell activation. Blockade of the by systemic administration small molecules significantly attenuated therapeutic efficacy decreased infiltration immune cells. In contrast, an mimic markedly increased enhanced cells vivo. High expression positively correlated with recruitment DCs T within tumor microenvironment associated favorable survival outcomes CRC patients who received adjuvant chemotherapy. Furthermore, loss-of-function mutation reduced CD8

Язык: Английский

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Targeting Mitochondrial Dysfunction in Cerebral Ischemia: Advances in Pharmacological Interventions

Antioxidants, Год журнала: 2025, Номер 14(1), С. 108 - 108

Опубликована: Янв. 18, 2025

The study of mitochondrial dysfunction has become increasingly pivotal in elucidating the pathophysiology various cerebral pathologies, particularly neurodegenerative disorders. Mitochondria are essential for cellular energy metabolism, regulation reactive oxygen species (ROS), calcium homeostasis, and execution apoptotic processes. Disruptions function, driven by factors such as oxidative stress, excitotoxicity, altered ion balance, lead to neuronal death contribute cognitive impairments several brain diseases. Mitochondrial can arise from genetic mutations, ischemic events, hypoxia, other environmental factors. This article highlights critical role progression diseases discusses need targeted therapeutic strategies attenuate damage, restore enhance neuroprotection.

Язык: Английский

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Interplay between Cell Death and Cell Proliferation Reveals New Strategies for Cancer Therapy

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(9), С. 4723 - 4723

Опубликована: Апрель 25, 2022

Cell division and cell death are fundamental processes governing growth development across the tree of life. This relationship represents an evolutionary link between cycle programs that is present in all cells. Cancer characterized by aberrant regulation both, leading to unchecked proliferation replicative immortality. Conventional anti-cancer therapeutic strategies take advantage proliferative dependency cancer yet, doing so, triggering apoptosis, a pathway which inherently resistant. A thorough understanding how therapeutics kill cells needed develop novel, more durable treatment strategies. While evolves cell-intrinsic resistance physiological pathways, there opportunities for agnostic forms death, example, necroptosis or ferroptosis. Furthermore, independent immunogenic, potentially licensing host immunity additional antitumor activity. Identifying vulnerabilities critical developing alternative can overcome resistance.

Язык: Английский

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MSCs-derived apoptotic extracellular vesicles promote muscle regeneration by inducing Pannexin 1 channel-dependent creatine release by myoblasts

International Journal of Oral Science, Год журнала: 2023, Номер 15(1)

Опубликована: Янв. 16, 2023

Abstract Severe muscle injury is hard to heal and always results in a poor prognosis. Recent studies found that extracellular vesicle-based therapy has promising prospects for regeneration medicine, however, whether vesicles have therapeutic effects on severe still unknown. Herein, we extracted apoptotic derived from mesenchymal stem cells (MSCs-ApoEVs) treat cardiotoxin induced tibialis anterior (TA) MSCs-ApoEVs promoted muscles increased the proportion of multinucleated cells. Besides that, also apoptosis was synchronized during myoblasts fusion ratio as well index myoblasts. Furthermore, revealed relative level creatine fusion, which released via activated Pannexin 1 channel. Moreover, channel highly expressed membrane myoblasts-derived ApoEVs (Myo-ApoEVs) instead myoblasts, pivotal metabolite involved fusion. Collectively, our findings firstly can promote elucidated new function passing inter-cell messages through releasing metabolites channel, will provide evidence vesicles-based improving understanding functions vesicles.

Язык: Английский

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SLC5A3 depletion promotes apoptosis by inducing mitochondrial dysfunction and mitophagy in gemcitabine-resistant pancreatic cancer cells

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Март 7, 2025

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor prognosis, largely due to the rapid development of chemoresistance in patients. Mitochondrial dynamics play crucial role cell survival. Currently, specific mechanisms underlying gemcitabine resistance PDAC remain unknown. In this study, we identified sodium/myo-inositol co-transporter solute carrier family 5 member 3 (SLC5A3) as key modulator promoting PDAC. SLC5A3 levels were significantly upregulated gemcitabine-resistant cells, enhancing their survival by stabilizing mitochondrial functions and inhibiting apoptosis. analysis showed that inhibition disrupted dynamics, leading increased reactive oxygen species production, fission, impaired oxidative phosphorylation. Moreover, activated PTEN-induced kinase 1/Parkin-mediated mitophagy pathway, resulting excessive removal damaged healthy mitochondria, thereby depleting reserves sensitizing cells vivo studies revealed targeting enhanced efficacy reduced tumor growth. Collectively, these results suggest SLC5A3-mediated regulation promising therapeutic strategy overcome

Язык: Английский

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Inactivation behavior and intracellular changes in Escherichia coli during electro-oxidation process using Ti/Sb–SnO2/PbO2 anode: Elucidation of the disinfection mechanism

Environmental Research, Год журнала: 2022, Номер 210, С. 112749 - 112749

Опубликована: Фев. 3, 2022

Язык: Английский

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Effect of Fluoride on Cytotoxicity Involved in Mitochondrial Dysfunction: A Review of Mechanism

Frontiers in Veterinary Science, Год журнала: 2022, Номер 9

Опубликована: Апрель 19, 2022

Fluoride is commonly found in the soil and water environment may act as chronic poison. A large amount of fluoride deposition causes serious harm to ecological human health. Mitochondrial dysfunction a shared feature fluorosis, numerous studies reported this phenomenon different model systems. More more evidence shows that functions mitochondria play an extremely influential role organs tissues after fluorosis. invades into cells mainly damages mitochondria, resulting decreased activity mitochondrial related enzymes, weakening protein expression, damage respiratory chain, excessive fission, disturbance fusion, disorder calcium regulation, decrease intracellular ATP accumulation Reactive oxygen species. At same time, membrane potential leads release Cyt c, causing series caspase cascade reactions apoptosis. This article reviews mechanism cytotoxicity caused by such dynamics, species, autophagy apoptosis, fusion disturbance, regulation are emphasized, effect on further explored.

Язык: Английский

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Structure versus function: Are new conformations of pannexin 1 yet to be resolved?

The Journal of General Physiology, Год журнала: 2021, Номер 153(5)

Опубликована: Апрель 9, 2021

Pannexin 1 (Panx1) plays a decisive role in multiple physiological and pathological settings, including oxygen delivery to tissues, mucociliary clearance airways, sepsis, neuropathic pain, epilepsy. It is widely accepted that Panx1 exerts its the context of purinergic signaling by providing transmembrane pathway for ATP. However, under certain conditions, can also act as highly selective membrane channel chloride ions without ATP permeability. A recent flurry publications has provided structural information about channel. while these structures are consistent with channel, none show conformation strong support release function Panx1. In this Viewpoint, we critically assess existing evidence structure conclude corresponding permeation yet be determined. We list set additional topics needing attention propose ways attain large-pore, ATP-permeable

Язык: Английский

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Crosstalk between the mTOR and Hippo pathways

Development Growth & Differentiation, Год журнала: 2023, Номер 65(6), С. 337 - 347

Опубликована: Май 20, 2023

Abstract Cell behavior changes in response to multiple stimuli, such as growth factors, nutrients, and cell density. The mechanistic target of the rapamycin (mTOR) pathway is activated by factors nutrient stimuli regulate autophagy, whereas Hippo has negative effects on proliferation tissue density, DNA damage, hormonal signals. These two signaling pathways must be precisely regulated integrated for proper behavior. This integrative mechanism not completely understood; nevertheless, recent studies have suggested that components mTOR interact with each other. Herein, per contemporary knowledge, we review molecular mechanisms interaction between mammals Drosophila . Moreover, discuss advantage this terms consumption.

Язык: Английский

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