Metabolic Rewiring in the Face of Genomic Assault: Integrating DNA Damage Response and Cellular Metabolism

Biomolecules, Год журнала: 2025, Номер 15(2), С. 168 - 168

Опубликована: Янв. 23, 2025

The DNA damage response (DDR) and cellular metabolism exhibit a complex, bidirectional relationship crucial for maintaining genomic integrity. Studies across multiple organisms, from yeast to humans, have revealed how cells rewire their in damage, supporting repair processes homeostasis. We discuss immediate metabolic shifts upon detection long-term reprogramming sustained stability, highlighting key signaling pathways participating molecules. Importantly, we examine can conversely induce changes oxidative stress through specific mechanisms, including the histone H2A variant X (H2AX)/ataxia telangiectasia mutated (ATM)/NADPH oxidase 1 (Nox1) pathway repair-specific ROS signatures. review covers organelle-specific responses adaptations associated with different primary focus on human cells. explore implications of this DDR–metabolism crosstalk cancer, aging, neurodegenerative diseases, emerging therapeutic opportunities. By integrating recent findings, provides comprehensive overview intricate interplay between DDR metabolism, offering new perspectives resilience potential avenues intervention.

Язык: Английский

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Study on the mechanism of Huangqi Chifeng Decoction regulating ferroptosis inhibiting smooth muscle cells derived foam cell formation

Journal of Ethnopharmacology, Год журнала: 2025, Номер unknown, С. 119507 - 119507

Опубликована: Фев. 1, 2025

Язык: Английский

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Disulfidptosis: a new target for central nervous system disease therapy

Frontiers in Neuroscience, Год журнала: 2025, Номер 19

Опубликована: Март 5, 2025

Disulfidptosis is a pathologic process that occurs under conditions of NADPH deficiency and excess disulfide bonds in cells express high levels SLC7A11. This caused by glucose deprivation-induced stress was first described cancer researchers. Oxidative hypothesized mechanism underlying diseases the central nervous system (CNS), specific type oxidative stress. Proteins linked to disulfidptosis metabolic pathways involved are significantly associated with CNS (neurodegenerative disease, neurogliomas ischemic stroke). However, responsible for this correlation remains unknown. review provides comprehensive overview current knowledge regarding origin elements, genetic factors, signaling proteins pathogenesis disulfidptosis. It demonstrates disruption thiometabolism play critical roles diseases, which potential role We also summarize disulfidptosis-related drugs highlight therapeutic strategies treating diseases. Additionally, paper suggests testable hypothesis might be promising target

Язык: Английский

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Green Tea Polyphenol Epigallocatechin-3-gallate Mediates an Antioxidant Response via Nrf2 Pathway in Heat-Stressed Poultry: A Review

Poultry Science, Год журнала: 2025, Номер 104(5), С. 105071 - 105071

Опубликована: Март 20, 2025

Heat stress is a critical challenge in the poultry industry. It arises when birds are exposed to elevated ambient temperatures beyond their thermoneutral zone, often exacerbated by high humidity and inadequate ventilation. This condition disrupts birds' ability maintain thermal homeostasis, leading physiological behavioral changes such as increased panting, reduced feed intake, water consumption. These responses aim dissipate heat but result energy imbalances, oxidative stress, impaired immune function. Green tea polyphenols (GTPs) mitigate modulating pathways, primarily scavenging reactive oxygen species (ROS) enhancing antioxidant defense mechanisms. pathways play pivotal role neutralizing ROS generated during inflammation, exposure electrophilic compounds. action helps restore cellular balance enhances overall mechanisms converting harmful free radicals into less molecules, oxygen. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) plays significant character activation of enzymatic antioxidants network. translocates nucleus upon activation, binds response elements (AREs) promoter regions target genes, upregulates expression key enzymes. Therefore, regulation Nrf2 considered molecular marker mitigating effects its detoxification enzymes, protecting against damage inflammation induced temperatures. exploratory review summarizes anti-oxidative GTPs poultry. highlights cytoprotective basis epigallocatechin-3-gallate (EGCG), particularly Nrf2-mediated which enhance systems protect damage.

Язык: Английский

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Oxidant-Based Cytotoxic Agents During Aging: From Disturbed Energy Metabolism to Chronic Inflammation and Disease Progression

Biomolecules, Год журнала: 2025, Номер 15(4), С. 547 - 547

Опубликована: Апрель 9, 2025

In humans, aging is an inevitable consequence of diminished growth processes after reaching maturity. The high order biomolecules in cells and tissues continuously disturbed by numerous physical chemical destructive impacts. Host-derived oxidant-based cytotoxic agents (reactive species, transition free metal ions, heme) contribute considerably to this damage. These are under the control immediately acting antagonizing principles, which important ensure cell tissue homeostasis. review, I apply concept host-derived their interplay with principles process. During aging, energy metabolism supply dioxygen nutrients increasingly disturbed. addition, a chronic inflammatory state develops, condition known as inflammaging. balance between protective mechanisms analyzed depending on age-based physiological alterations ATP production. Disturbances associated development age-related diseases comorbidities. An enhanced production reactive species from dysfunctional mitochondria, cellular redox homeostasis, adaptations hypoxia highlighted. Examples how disturbances pathogenesis persons advanced age given.

Язык: Английский

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Apoplastic pH is a chemical switch for extracellular H₂O₂ signaling in abscisic acid‐mediated inhibition of cotyledon greening

New Phytologist, Год журнала: 2025, Номер unknown

Опубликована: Янв. 20, 2025

Summary The apoplastic pH (pH Apo ) in plants is susceptible to environmental stimuli. However, the biological implications of variation have remained largely unknown. universal stress phytohormone abscisic acid (ABA) as well major stimuli drought and salinity were selected representative cases investigate how changes relate plant behaviors Arabidopsis . Variations negatively regulated cotyledon greening inhibition hormone ABA or through action extracellular hydrogen peroxide (eH 2 O ). Further studies revealed that an increase diminishes chemical reactivity eH , effectively functioning ‘off’ switch for its oxidizing thiols plasma membrane proteins. Consequently, this suppresses ‐mediated ABA, alongside inhibiting intracellular Ca 2+ signaling. Conversely, a decrease serves ‘on’ In summary, crucial messenger signal transduction, notwithstanding apparent simplicity underlying mechanism. Our findings provide novel fundamental insight into significance pH.

Язык: Английский

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ChPDIA3 targeted by miR-126-x and miR-21-y responds to Vibrio harveyi infection in Crassostrea hongkongensis

Frontiers in Cellular and Infection Microbiology, Год журнала: 2025, Номер 15

Опубликована: Фев. 14, 2025

Introduction The Hong Kong oyster ( Crassostrea hongkongensis ), as the main marine aquaculture shellfish in South China Sea, not only has high economic and ecological value, but also is an ideal model for conducting research on pathogen-host interactions. In cultivation process of C. , there a challenge posed by vibrios . To improve antibacterial strains we have studied gene associated with immunity, PDIA3 Methods findings this study, cloned sequence using RACE technique. It total 2081 bp contains 5'-UTR 55 3'-UTR 547 bp. ChPDIA3 ORF frame that 1479 length encodes 492 amino acids. Analysis phylogenetic tree constructed Neighbor Joining method showed clustered other shellfishes into single unit, which was consistent law species evolution. Discussion highest expression detected gill tissues RT-qPCR, significantly higher V. harveyi LPS infection than Poly(I:C) P <0.05). This may indicate primarily involved immune response against bacterial infections binding sites miR-126-x, miR-21-y were dual luciferase experiments, respectively. results both miR-126-x inhibited region suggested expression. study will help to further understand function pathogen infection, thus providing new ideas understanding resistance adaptation Vibrio infection.

Язык: Английский

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Redox Regulation of cAMP-Dependent Protein Kinase and Its Role in Health and Disease

Life, Год журнала: 2025, Номер 15(4), С. 655 - 655

Опубликована: Апрель 16, 2025

Protein kinase A (PKA) is a key regulator of cellular signaling that regulates physiological processes such as metabolism, cell proliferation, and neuronal function. While its activation by the second messenger 3′,5′-cyclic adenosine triphosphate (cAMP) well characterized, recent research highlights additional regulatory mechanisms, particularly oxidative post-translational modifications, influence PKA’s structure, activity, substrate specificity. Both catalytic subunits PKA are susceptible to redox which have been shown play important roles in regulation functions, including cardiac contractility, lipid immune response. Likewise, redox-dependent modulation has implicated numerous diseases, cardiovascular disorders, diabetes, neurodegenerative conditions, making it potential therapeutic target. However, mechanisms crosstalk between redox- PKA-dependent remain poorly understood. This review examines structural functional PKA, with focus on modifications their impact signaling. deeper understanding these may provide new strategies for targeting stress disease restoring balanced cells.

Язык: Английский

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Pristimerin inhibits thioredoxin reductase in the treatment of non-small cell lung cancer

Acta Materia Medica, Год журнала: 2024, Номер 3(2)

Опубликована: Янв. 1, 2024

Elevated cellular oxidative stress is a common marker of cancer cell dysregulation caused by malignant transformation. Thioredoxin reductase (TrxR, encoded TXNRD ) crucial enzyme that regulates and the survival many types cells. Therefore, targeting TrxR may lead to selective death in Pristimerin, plant triterpenoid, increases accumulation reactive oxygen species (ROS) cells, but its specific regulatory mechanism unclear. Herein, we found pristimerin selectively targets subsequently induces apoptosis human non-small lung inhibits tumor growth vivo with low toxicity normal Pristimerin was inhibit primarily inhibiting TrxR, thereby compromising TrxR’s antioxidant function cells resulting oxidized Trx. Furthermore, excessive ROS stimulated triggered tumor-specific amplification ultimately led targeted destruction Our data support development potential therapeutic molecules as anticancer agents highly enriched

Язык: Английский

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Aerobic exercise alleviates skeletal muscle aging in male rats by inhibiting apoptosis via regulation of the Trx system

Experimental Gerontology, Год журнала: 2024, Номер 194, С. 112523 - 112523

Опубликована: Июль 18, 2024

Skeletal muscle aging in rats is a reduction skeletal mass caused by decrease the number or volume of myofibers. Apoptosis has been recognized to play key role accelerating process rats. The thioredoxin (Trx) system widely expressed oxidoreductase that controls cellular reduction/oxidation state and both potent anti-free radical damage important pro-growth apoptosis inhibitory functions. Previous studies have shown exercise delays aging. However, it unclear whether attenuates via Trx system. Therefore, present study used as an entry point explore effect aerobic improve its possible mechanisms, provide theoretical basis for delay It was senescent resulted increased gastrocnemius index, decreased body weight, endurance, cell apoptosis, activity protein expression system, p38 ASK1. Based on these findings, we conclude 10 weeks may enhance anti-apoptotic up-regulating reductase (TR) expression, which turn increases rat muscle, ultimately alleviates cells.

Язык: Английский

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