Fundamentals of redox regulation in biology

Nature Reviews Molecular Cell Biology, Год журнала: 2024, Номер 25(9), С. 701 - 719

Опубликована: Апрель 30, 2024

Язык: Английский

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Lung cancer associated with combustion particles and fine particulate matter (PM2.5) - The roles of polycyclic aromatic hydrocarbons (PAHs) and the aryl hydrocarbon receptor (AhR)

Biochemical Pharmacology, Год журнала: 2023, Номер 216, С. 115801 - 115801

Опубликована: Сен. 9, 2023

Air pollution is the leading cause of lung cancer after tobacco smoking, contributing to 20% all deaths. Increased risk associated with living near trafficked roads, occupational exposure diesel exhaust, indoor coal combustion and cigarette suggest that components in ambient fine particulate matter (PM2.5), such as polycyclic aromatic hydrocarbons (PAHs), may be central drivers cancer. Activation aryl hydrocarbon receptor (AhR) induces expression xenobiotic-metabolizing enzymes (XMEs) increase PAH metabolism, formation reactive metabolites, oxidative stress, DNA damage mutagenesis. Lung tissues from smokers workers exposed high PM levels contain mutagenic signatures derived PAHs. However, recent findings air PM2.5 primarily development through tumor promotion cells harboring naturally acquired oncogenic mutations, thus lacking typical PAH-induced mutations. On this background, we discuss role AhR PAHs caused by focusing on promoting properties including immune system, cell proliferation survival, microenvironment, cell-to-cell communication, growth metastasis. We dichotomy patterns observed between smoking outdoor represent two ends a dose–response continuum exposure, where peripheral appears driving factor at relatively low-dose exposures PM2.5, whereas genotoxicity airways becomes increasingly more important higher encountered exposure.

Язык: Английский

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Toxicity of airborne nanoparticles: Facts and challenges

Environment International, Год журнала: 2024, Номер 190, С. 108889 - 108889

Опубликована: Июль 18, 2024

Air pollution is one of the most severe environmental health hazards, and airborne nanoparticles (diameter <100 nm) are considered particularly hazardous to human health. They produced by various sources such as internal combustion engines, wood biomass burning, fuel natural gas combustion, their origin, among other parameters, determines intrinsic toxicity for reasons that not yet fully understood. Many constituents toxic or at least hazardous, including polycyclic aromatic hydrocarbons (PAHs) heavy metal compounds, in addition gaseous pollutants present aerosol fraction, NOx, SO2, ozone. All these compounds can cause oxidative stress, mitochondrial damage, inflammation lungs tissues, cellular organelles. Epidemiological investigations concluded may affect respiratory, cardiovascular, nervous systems. Moreover, particulate matter has been linked an increased risk lung cancer, a carcinogenic effect related DNA but inflammatory response pollutants, which release cytokines promotes proliferation pre-existing mutated cancer cells. The mechanisms behind be investigated experimentally using cell cultures animal models. Methods gathering have explored, standardized protocols needed ensure samples accurately represent chemical mixtures environment. Toxic studied models, designing realistic exposure settings challenging. air–liquid interface (ALI) system directly exposes cells, mimicking particle inhalation into lungs. Continuous research monitoring essential understanding effects developing active strategies mitigate risks

Язык: Английский

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Air pollution and skin diseases: A comprehensive evaluation of the associated mechanism

Ecotoxicology and Environmental Safety, Год журнала: 2024, Номер 278, С. 116429 - 116429

Опубликована: Май 7, 2024

Air pollutants deteriorate the survival environment and endanger human health around world. A large number of studies have confirmed that air pollution jeopardizes multiple organs, such as cardiovascular, respiratory, central nervous systems. Skin is largest organ first barrier protects us from outside particulate matter (PM), polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs) will affect structure function skin bring about development inflammatory diseases (atopic dermatitis (AD), psoriasis), accessory (acne, alopecia), auto-immune (cutaneous lupus erythematosus(CLE) scleroderma), even tumors (melanoma, basal cell carcinoma (BCC), squamous-cell (SCC)). Oxidative stress, damage, microbiome dysbiosis, inflammation are pathogenesis stimulation. In this review, we summarize current evidence on effects possible mechanisms to provide strategies for future research.

Язык: Английский

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Structural basis for the ligand-dependent activation of heterodimeric AHR-ARNT complex

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 3, 2025

The aryl hydrocarbon receptor (AHR) possesses an extraordinary capacity to sense and respond a wide range of small-molecule ligands, ranging from polycyclic aromatic hydrocarbons endogenous compounds. Upon ligand binding, AHR translocates the cytoplasm nucleus, forming transcriptionally active complex with nuclear translocator (ARNT), for DNA binding initiation gene expression programs that include cellular detoxification pathways immune responses. Here, we examine molecular mechanisms governing AHR's high-affinity activation by diverse group ligands. Crystal structures AHR-ARNT-DNA complexes, bound each six established including Tapinarof, 6-formylindolo[3,2-b]carbazole (FICZ), benzo[a]pyrene (BaP), β-naphthoflavone (BNF), Indigo Indirubin, reveal unconventional mode subunit assembly intimate association between PAS-B domains ARNT. domain utilizes eight conserved residues whose dynamic rearrangements account ability bind ligands through hydrophobic π-π interactions. Our findings further structural underpinnings ligand-driven mechanism, whereby segment protein undergoes transition chaperone engagement ARNT heterodimer stabilization, generate competent assembly. results provide key information future development AHR-targeting drugs.

Язык: Английский

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The complex biology of aryl hydrocarbon receptor activation in cancer and beyond

Biochemical Pharmacology, Год журнала: 2023, Номер 216, С. 115798 - 115798

Опубликована: Сен. 9, 2023

The aryl hydrocarbon receptor (AHR) signaling pathway is a complex regulatory network that plays critical role in various biological processes, including cellular metabolism, development, and immune responses. complexity of AHR arises from multiple factors, the diverse ligands activate receptor, expression level itself, its interaction with nuclear translocator (ARNT). Additionally, crosstalks repressor (AHRR) or other transcription factors pathways it can also mediate non-genomic effects. Finally, posttranslational modifications partners, epigenetic regulation target genes, as well AHR-mediated induction enzymes degrade AHR-activating may contribute to context-specificity activation. Understanding crucial for deciphering physiological pathological roles developing therapeutic strategies targeting this pathway. Ongoing research continues unravel intricacies signaling, shedding light on mechanisms controlling functions.

Язык: Английский

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Transcription Factor AhR Regulates Glutathione S-Transferases Conferring Resistance to lambda-Cyhalothrin in Cydia pomonella

Journal of Agricultural and Food Chemistry, Год журнала: 2023, Номер 71(13), С. 5230 - 5239

Опубликована: Март 21, 2023

Aryl hydrocarbon receptor (AhR) enhances insect resistance to insecticides by regulating the detoxification network. Our previous studies have confirmed that overexpressions of cytochrome P450 monooxygenases (P450s) and glutathione S-transferases (GSTs) are involved in lambda-cyhalothrin Cydia pomonella. Here, we report CpAhR regulates expression GST genes, thus conferring resistance. Expression patterns indicated was highly induced exposure upregulated a lambda-cyhalothrin-resistant population. RNA interference (RNAi) decreases key resistance-related genes (CpGSTe3, CpCYP9A121, CpCYP9A122) activity enzyme, reducing tolerance lambda-cyhalothrin. Furthermore, β-naphthoflavone, novel agonist AhR, first proven be effective increasing larval These results demonstrate detoxifying activity, resulting development C.

Язык: Английский

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Indole derivatives ameliorated the methamphetamine-induced depression and anxiety via aryl hydrocarbon receptor along “microbiota-brain” axis

Gut Microbes, Год журнала: 2025, Номер 17(1)

Опубликована: Фев. 25, 2025

In addition to the high neurotoxicity, depression, and anxiety are most prominent characteristics of methamphetamine (Meth) withdrawal. Studies date on issue Meth-associated depression focused brain, however, whether peripheral homeostasis, especially "microbiota-gut" axis participates in these adverse outcomes, remains poorly understood. current study, with fecal microbiota transplantation (FMT) assay, mice received from Meth withdrawal displayed marked behaviors. The 16S rRNA sequencing results showed that contributed a striking reduction Akkermansia, Bacteroides, Faecalibaculum, Desulfovibrio, Anaerostipes, which known be associated tryptophan (TRP) metabolism. Noteworthily, substantial decreases indole derivatives TRP metabolic pathway, including IAA, IPA, ILA, IET, IArA, IAld, TRM were observed serum both abusing humans during UHPLC-MS/MS analysis. Combining low diet mouse model, obviously impeded behaviors, further strengthened by evidence administration dramatically ameliorated induced aberrant Importantly, protective effects remarkably counteracted aryl hydrocarbon receptor knockout (AhR KO) mice, underlining key roles microbiota-indoles-AhR signaling anxiety. Collectively, important contribution present work is we provide first gut homeostasis disturbance but not limited plays role driving Meth-induced periods withdrawal, disturbance. Therefore, targeting AhR may novel insight into therapeutic strategies for psychological disorders.

Язык: Английский

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The AHR–NRF2–JDP2 gene battery: Ligand–induced AHR transcriptional activation

Biochemical Pharmacology, Год журнала: 2025, Номер 233, С. 116761 - 116761

Опубликована: Янв. 23, 2025

Язык: Английский

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The Role of Aryl Hydrocarbon Receptor in Skin Homeostasis: Implications for Therapeutic Strategies in Skin Disorders

Cell Biochemistry and Function, Год журнала: 2025, Номер 43(2)

Опубликована: Янв. 27, 2025

ABSTRACT The aryl hydrocarbon receptor (AhR), a ligand‐activated transcription factor, is extensively expressed in diverse human organs and plays pivotal role mediating the onset, progression, severity of numerous diseases. Recent research has explored substantial impact AhR on skin homeostasis related pathologies. As multi‐layered organ, comprises multiple cell populations that express AhR. In this review, we introduce various cells its barrier function. Furthermore, explore involvement development diseases, highlighting potential as therapeutic target for disorders. By targeting AhR, may open new avenues novel efficient disease treatments.

Язык: Английский

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