ArticleThe American journal of pathology2015
NADPH Oxidase-Derived Peroxynitrite Drives Inflammation in Mice and Human Nonalcoholic Steatohepatitis via TLR4-Lipid Raft Recruitment.
Article in The American journal of pathology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 53 citations in OpenAlex.
- Circulating GPER-1, 8-Iso-Prostaglandin FJournal of clinical medicine · 2026Article
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Obesity-Associated NAFLD Coexists with a Chronic Inflammatory Kidney Condition That Is Partially Mitigated by Short-Term Oral Metformin.Nutrients · 2025Article
- Targeting the STAT3/ACLY axis attenuates pulmonary inflammation but delays Mycoplasma pneumoniae clearance via citrate metabolism.Medical microbiology and immunology · 2025Article
- The Impact of Recreational Diving to a Depth of 40 m on Selected Intracellular DAMPs.International journal of molecular sciences · 2025Article
- Mechanisms of rifaximin inhibition of hepatic fibrosis in mice with metabolic dysfunction associated steatohepatitis through the TLR4/NFκB pathway.Scientific reports · 2025Article
- Small molecule probes for peroxynitrite detection.Redox biochemistry and chemistry · 2024Article
- Causal relationship between air pollution, lung function, gastroesophageal reflux disease, and non-alcoholic fatty liver disease: univariate and multivariate Mendelian randomization study.Frontiers in public health · 2024Article
- Uric Acid: A Translational Journey in Cerebroprotection That Spanned Preclinical and Human Data.Neurology · 2023Review
- NO-IL-6/10-IL-1β axis: a new pathway in steatotic and non-steatotic liver grafts from brain-dead donor rats.Frontiers in immunology · 2023Article
- Targeting fibrosis, mechanisms and cilinical trials.Signal transduction and targeted therapy · 2022Review
- Article
- Nonalcoholic fatty liver disease (NAFLD) from pathogenesis to treatment concepts in humans.Molecular metabolism · 2021Review
- Higher intestinal and circulatory lactate associated NOX2 activation leads to an ectopic fibrotic pathology following microcystin co-exposure in murine fatty liver disease.Comparative biochemistry and physiology. Toxicology & pharmacology : CBP · 2020Article
- Article
- Saturated Fatty Acids in Obesity-Associated Inflammation.Journal of inflammation research · 2020Review
- Environmental microcystin targets the microbiome and increases the risk of intestinal inflammatory pathology via NOX2 in underlying murine model of Nonalcoholic Fatty Liver Disease.Scientific reports · 2019Article
- Redox Regulation of Metabolic Syndrome: Recent Developments in Skeletal Muscle Insulin Resistance and Non-alcoholic Fatty Liver Disease (NAFLD).Current opinion in physiology · 2019Article
- Five Constituents inFrontiers in pharmacology · 2019Article
- Toxicity of polycyclic aromatic hydrocarbons involves NOX2 activation.Toxicology reports · 2019Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
The molecular events that link NADPH oxidase activation and the induction of Toll-like receptor (TLR)-4 recruitment into hepatic lipid rafts in nonalcoholic steatohepatitis (NASH) are unclear. We hypothesized that in liver, NADPH oxidase activation is key in TLR4 recruitment into lipid rafts, which in turn up-regulates NF-κB translocation to the nucleus and subsequent DNA binding, leading to NASH progression. Results from confocal microscopy showed that liver from murine and human NASH had NADPH oxidase activation, which led to the formation of highly reactive peroxynitrite, as shown by 3-nitrotyrosine formation in diseased liver. Expression and recruitment of TLR4 into the lipid rafts were significantly greater in rodent and human NASH. The described phenomenon was NADPH oxidase, p47phox, and peroxynitrite dependent, as liver from p47phox-deficient mice and from mice treated with a peroxynitrite decomposition catalyst [iron(III) tetrakis(p-sulfonatophenyl)porphyrin] or a peroxynitrite scavenger (phenylboronic acid) had markedly less Tlr4 recruitment into lipid rafts. Mechanistically, peroxynitrite-induced TLR4 recruitment was linked to increased IL-1β, sinusoidal injury, and Kupffer cell activation while blocking peroxynitrite-attenuated NASH symptoms. The results strongly suggest that NADPH oxidase-mediated peroxynitrite drove TLR4 recruitment into hepatic lipid rafts and inflammation, whereas the in vivo use of the peroxynitrite scavenger phenylboronic acid, a novel synthetic molecule having high reactivity with peroxynitrite, attenuates inflammatory pathogenesis in NASH.
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