Lactate facilitated mitochondrial fission-derived ROS to promote pulmonary fibrosis via ERK/DRP-1 signaling

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Май 21, 2024

Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung diseases, which mainly existed in middle-aged and elderly people. The accumulation of reactive oxygen species (ROS) common characteristic IPF. Previous research also shown that lactate levels can be abnormally elevated IPF patients. Emerging evidence suggested relationship between ROS needs further elucidation. In this article, we utilized mouse model BLM-induced to detect alterations other indicators associated with fibrosis. Lactate could induce mitochondrial fragmentation by modulating expression activity DRP1 ERK. Moreover, Increased promoted P65 translocation into nucleus, leading markers. Finally, Ulixertinib, Mdivi-1 Mito-TEMPO, were inhibitor ERK, mtROS, respectively, effectively prevented damage production eventually alleviate Taken together, these findings promote increasing fission-derived via ERK/DRP1 signaling, may provide novel therapeutic solutions for

Язык: Английский

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Lactate-induced protein lactylation in cancer: functions, biomarkers and immunotherapy strategies

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 10, 2025

Lactate, long viewed as a byproduct of glycolysis and metabolic waste. Initially identified within the context yogurt fermentation, lactate's role extends beyond culinary applications to its significance in biochemical processes. Contemporary research reveals that lactate functions not merely terminal product but also nexus for initiating physiological pathological responses body. Lysine lactylation (Kla), novel post-translational modification (PTM) proteins, has emerged pivotal mechanism by which exerts regulatory influence. This epigenetic potential alter gene expression patterns, thereby impacting Increasing evidence indicates correlation between adverse prognosis various malignancies. Consequently, this review article aims encapsulate proteins interact with lactate, elucidate tumorigenesis progression, explore therapeutic targets afforded modulation lactylation. The objective is clarify oncogenic provide strategic framework future directions burgeoning field.

Язык: Английский

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Feline Calicivirus Infection Manipulates Central Carbon Metabolism

Veterinary Sciences, Год журнала: 2025, Номер 12(2), С. 138 - 138

Опубликована: Фев. 7, 2025

Viruses can manipulate the host metabolism to achieve optimal replication conditions, and central carbon (CCM) pathways are often crucial in determining viral infections. Feline calicivirus (FCV), a diminutive RNA agent, induces upper respiratory tract infections feline hosts, with highly pathogenic strains capable of precipitating systemic subsequent cell necrosis, thereby presenting formidable challenge survival protection. However, relationship between FCV remains unclear, precise mechanisms yet be elucidated. Upon infection Crandell-Rees Kidney (CRFK) cells, an enhanced cellular uptake glucose glutamine was observed. Metabolomics analyses disclosed pronounced alterations infected cells. found augment glycolytic activity while sustaining tricarboxylic acid (TCA) cycle flux, ATP levels remaining invariant. Concurrently, both flux pentose phosphate pathway (PPP) were noted intensified. The application various inhibitory agents targeting glycolysis, metabolism, PPP resulted significant suppression proliferation. Experiments involving deprivation demonstrated that absence either nutrient markedly curtailed replication. Collectively, these findings suggest critical interplay stimulates CRFK cells uptake, supplying necessary metabolic substrates energy for During infection, emerges as primary substrate, ensuring production homeostasis, is predominantly channeled into facilitate nucleotide synthesis.

Язык: Английский

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The Seneca Valley virus 3C protease cleaves DCP1A to attenuate its antiviral effects

Veterinary Research, Год журнала: 2025, Номер 56(1)

Опубликована: Фев. 28, 2025

Abstract Seneca Valley virus (SVV), a new member of Picornaviridae , causes idiopathic vesicular symptoms in pregnant sows and acute death neonatal piglets, considerably damaging the swine industry. The viral protease 3C (3C pro ) cleaves host immune-related molecules to create favorable environment for replication. In this study, we found that mRNA decapping enzyme 1A (DCP1A) is novel antiviral effector against SVV infection targets 3D RNA-dependent RNA polymerase OPTN-mediated autophagic degradation. To counteract effect, DCP1A cleavage at glutamine 343 (Q343), resulting cleaved products (1–343) (344–580), which lose ability restrict contrast, cleavage-resistant DCP1A-Q343A mutant exhibited stronger effects than wild-type DCP1A. Additionally, degradation protein targeted by was abolished after its . conclusion, our study demonstrated pivotal ISG antagonist These results offer insight into how viruses evade immunity.

Язык: Английский

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circRNA_8521 promotes Senecavirus A infection by sponging miRNA-324 to regulate LC3A

Veterinary Research, Год журнала: 2024, Номер 55(1)

Опубликована: Апрель 5, 2024

Abstract Senecavirus A (SVA) causes outbreaks of vesicular disease in pigs, which imposes a considerable economic burden on the pork industry. As current SVA prevention measures are ineffective, new strategies for controlling urgently needed. Circular (circ)RNA is newly characterized class widely expressed, endogenous regulatory RNAs, have been implicated viral infection; however, whether circRNAs regulate infection remains unknown. To investigate influence porcine kidney 15 (PK-15) cells, RNA sequencing technology was used to analyze circRNA expression profiles SVA-infected and uninfected PK-15 interactions between circRNAs, miRNAs, mRNAs potentially were predicted using bioinformatics tools. The prediction accuracy verified quantitative real-time (qRT)-PCR, Western blotting, as well dual-luciferase reporter pull-down assays. results showed that 67 differentially expressed result infection. We found circ_8521 significantly upregulated cells promoted interacted with miR-324. miR-324 bound LC3A mRNA inhibited LC3A. Knockdown However, by binding miR-324, thereby promoting demonstrated functioned an sponge sequester ultimately

Язык: Английский

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ZBP1 inhibits the replication of Senecavirus A by enhancing NF-κB signaling pathway mediated antiviral response in porcine alveolar macrophage 3D4/21 cells

Cellular & Molecular Biology Letters, Год журнала: 2024, Номер 29(1)

Опубликована: Май 31, 2024

Abstract Background Senecavirus A (SVA) caused porcine idiopathic vesicular disease (PIVD) showing worldwide spread with economic losses in swine industry. Although some progress has been made on host factors regulating the replication of SVA, role Z-DNA binding protein 1 (ZBP1) remains unclear. Methods The expression ZBP1 SVA-infected 3D/421 cells was analyzed by quantitative real-time PCR (qRT-PCR) and western blot. Western blot qRT-PCR were used to detect effects over interference SVA VP2 gene protein. Viral growth curves prepared measure viral proliferation. effect type I interferons (IFNs), interferon-stimulated genes (ISGs), pro-inflammatory cytokines infection qRT-PCR. analysis NF-κB signaling pathway inhibitor are confirm. Results is shown inhibit enhancing mediated antiviral response. significantly up-regulated 3D4/21 cells. Infection overexpression showed that inhibited enhanced IFNs (IFN-α, IFN-β), ISGs (ISG15, PKR, IFIT1) (IL-6, IL-8, TNF-α), while, infected-cells opposite effects. Further results achieved activation specific also confirmed this. Conclusions an important factor indicates may be a novel target against SVA. Graphical

Язык: Английский

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Influenza A virus-induced glycolysis facilitates virus replication by activating ROS/HIF-1α pathway

Free Radical Biology and Medicine, Год журнала: 2024, Номер 225, С. 910 - 924

Опубликована: Ноя. 1, 2024

Язык: Английский

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TRIM26 facilitates PRV infection through NDP52-mediated autophagic degradation of MAVS

Veterinary Research, Год журнала: 2024, Номер 55(1)

Опубликована: Июль 4, 2024

Pseudorabies virus (PRV) has evolved multiple strategies to evade host antiviral responses benefit replication and establish persistent infection. Recently, tripartite motif 26 (TRIM26), a TRIM family protein, been shown be involved in broad range of biological processes innate immunity, especially regulating viral Herein, we found that the expression TRIM26 was significantly induced after PRV Surprisingly, overexpression promoted production, while depletion this protein inhibited replication, suggesting could positively regulate Further analysis revealed negatively regulates immune response by targeting RIG-I-triggered type I interferon signalling pathway. physically associated with MAVS independent infection reduced expression. Mechanistically, NDP52 interacted both TRIM26-induced degradation almost entirely blocked NDP52-knockdown cells, demonstrating degrades through NDP52-mediated selective autophagy. Our results reveal novel mechanism which escapes immunity provide insights into crosstalk among infection, autophagy, response.

Язык: Английский

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Brucella abortushijacks the host protein Slc2a1via the SepA effector to promote intracellular survival in macrophages

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Янв. 20, 2025

Brucella spp. are facultative intracellular bacteria that infect and induce brucellosis in a diverse range of mammalian hosts. The disease causes major global economic losses also is worldwide threat to public health security. Characterization bacterial host factors promote survival key for the prevention control brucellosis. In this study, we identified proteins involved Brucella abortus A19 RAW264.7 macrophage cells by liquid chromatography-mass spectrometry macrophages with or without B. infection. functions these proteins, signaling pathways which participate, domain entries enriched subcellular localization differentially-expressed were deciphered. Differential protein expression revealed Slc2a1, Glycolytic protein, was significantly upregulated infected cells. This observation confirmed qRT-PCR Western blotting studies. role Slc2a1 probed overexpressing knocking down SLC2A1 Overproduction promoted proliferation whereas knockdown inhibited bacterium. Finally, determined Secreted Effector Protein A (SepA) effector enhanced Thus, stimulates via SepA aid environment suggests may be novel antibacterial target combat

Язык: Английский

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Chicken C4BPM facilitates replication of H5N1 and H9N2 Avian Influenza Viruses by inhibiting the production of type I interferons

Poultry Science, Год журнала: 2025, Номер 104(3), С. 104868 - 104868

Опубликована: Янв. 31, 2025

Avian influenza viruses (AIVs) are potential pandemic of global concern, posing a major threat to both the poultry industry and human health. Host factors play key role in replication AIVs, while function complement component 4 binding protein, membrane (C4BPM) this process is still unclear. This research reports that C4BPM promotes H5N1 H9N2 AIVs by inhibiting type I interferons (IFNs). infection up-regulate expression chicken embryo fibroblast cells (DF-1). To verify knockout (C4BPM-KO) stable overexpressing (C4BPM-overexpressing) DF-1 were generated using lentivirus-mediated CRISPR/Cas9 gene editing technology molecular cloning strategies. Replication promoted C4BPM-overexpressing with inhibited IFNs (IFN-α, IFN-β), protein kinase R (PKR), cholesterol 25-hydroxylase (CH25H), interferon regulatory factor (IRF) 3, mitochondrial antiviral signaling (MAVS) compared cells. However, C4BPM-KO increased above related anti-viral factors. Further results showed did not affect viral adsorption, while, promote entry AIVs. These expand range host regulating suggest promising target for agent.

Язык: Английский

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