ArticleFree radical biology & medicine2012
P2X7 receptor-NADPH oxidase axis mediates protein radical formation and Kupffer cell activation in carbon tetrachloride-mediated steatohepatitis in obese mice.
Article in Free radical biology & medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 54 citations in OpenAlex.
- Neuroinflammatory control of metabolism in huntington's disease: central role of P2 × 7 receptor mediated redox lipid/epigenetic crosstalk.Inflammopharmacology · 2026Review
- Research Progress on Leptin in Metabolic Dysfunction-associated Fatty Liver Disease.Journal of clinical and translational hepatology · 2025Review
- Sterile inflammation in MASH: emerging role of extracellular RNA and therapeutic strategies.npj metabolic health and disease · 2025Review
- Purinergic signaling in liver disease: calcium signaling and induction of inflammation.Purinergic signalling · 2025Review
- Purinergic Signaling in Non-Parenchymal Liver Cells.International journal of molecular sciences · 2024Review
- P2rx1 deficiency alleviates acetaminophen-induced acute liver failure by regulating the STING signaling pathway.Cell biology and toxicology · 2023Article
- Review
- Knockout of Purinergic P2YInternational journal of molecular sciences · 2023Article
- Role of CaInternational journal of molecular medicine · 2022Review
- Purinergic signaling in the modulation of redox biology.Redox biology · 2021Review
- Review
- Purinergic Signaling in Liver Pathophysiology.Frontiers in endocrinology · 2021Review
- Purinergic signalling in liver diseases: Pathological functions and therapeutic opportunities.JHEP reports : innovation in hepatology · 2020Review
- P2X7 receptor deletion attenuates oxidative stress and liver damage in sepsis.Purinergic signalling · 2020Article
- Adenosine Triphosphate Accumulated Following Cerebral Ischemia Induces Neutrophil Extracellular Trap Formation.International journal of molecular sciences · 2020Article
- From overnutrition to liver injury: AMP-activated protein kinase in nonalcoholic fatty liver diseases.The Journal of biological chemistry · 2020Review
- Increased Purinergic Responses Dependent on P2Y2 Receptors in Hepatocytes from CClInternational journal of molecular sciences · 2020Article
- Reactive oxygen species play a role in P2X7 receptor-mediated IL-6 production in spinal astrocytes.Purinergic signalling · 2020Article
- Pharmacological inhibition of P2RX7 ameliorates liver injury by reducing inflammation and fibrosis.PloS one · 2020Article
- P2X7 Receptor Antagonist A804598 Inhibits Inflammation in Brain and Liver in C57BL/6J Mice Exposed to Chronic Ethanol and High Fat Diet.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2019Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
While some studies show that carbon tetrachloride-mediated metabolic oxidative stress exacerbates steatohepatitic-like lesions in obese mice, the redox mechanisms that trigger the innate immune system and accentuate the inflammatory cascade remain unclear. Here we have explored the role of the purinergic receptor P2X7-NADPH oxidase axis as a primary event in recognizing the heightened release of extracellular ATP from CCl(4)-treated hepatocytes and generating redox-mediated Kupffer cell activation in obese mice. We found that an underlying condition of obesity led to the formation of protein radicals and posttranslational nitration, primarily in Kupffer cells, at 24h post-CCl(4) administration. The free radical-mediated oxidation of cellular macromolecules, which was NADPH oxidase and P2X7 receptor-dependent, correlated well with the release of TNF-α and MCP-2 from Kupffer cells. The Kupffer cells in CCl(4)-treated mice exhibited increased expression of MHC Class II proteins and showed an activated phenotype. Increased expression of MHC Class II was inhibited by the NADPH oxidase inhibitor apocynin , P2X7 receptor antagonist A438709 hydrochloride, and genetic deletions of the NADPH oxidase p47 phox subunit or the P2X7 receptor. The P2X7 receptor acted upstream of NADPH oxidase activation by up-regulating the expression of the p47 phox subunit and p47 phox binding to the membrane subunit, gp91 phox. We conclude that the P2X7 receptor is a primary mediator of oxidative stress-induced exacerbation of inflammatory liver injury in obese mice via NADPH oxidase-dependent mechanisms.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.