ArticleAmerican journal of physiology. Cell physiology2012
Pannexin1 contributes to pathophysiological ATP release in lipoapoptosis induced by saturated free fatty acids in liver cells.
Article in American journal of physiology. Cell physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 65 citations in OpenAlex.
- Early urate-lowering therapy in gouty arthritis with acute flares: a double-blind placebo controlled clinical trial.European journal of medical research · 2023Trial
- PANX1-mediated ATP release confers FAM3A's suppression effects on hepatic gluconeogenesis and lipogenesis.Military Medical Research · 2024Article
- Pannexins in the musculoskeletal system: new targets for development and disease progression.Bone research · 2024Review
- Review
- Connexin 43 and Pannexin 1 hemichannels as endogenous regulators of innate immunity in sepsis.Frontiers in immunology · 2024Review
- Hepatic Macrophages as Targets for the MSC-Based Cell Therapy in Non-Alcoholic Steatohepatitis.Biomedicines · 2023Review
- Pannexin1 channels in the liver: an open enemy.Frontiers in cell and developmental biology · 2023Review
- Pannexin1: insight into inflammatory conditions and its potential involvement in multiple organ dysfunction syndrome.Frontiers in immunology · 2023Review
- Identification of MAP3K4 as a novel regulation factor of hepatic lipid metabolism in non-alcoholic fatty liver disease.Journal of translational medicine · 2022Article
- Mechanisms of Pannexin 1 (PANX1) Channel Mechanosensitivity and Its Pathological Roles.International journal of molecular sciences · 2022Review
- Expression of connexins and pannexins in diseased human liver.EXCLI journal · 2022Article
- Western Diet Decreases the Liver Mitochondrial Oxidative Flux of Succinate: Insight from a Murine NAFLD Model.International journal of molecular sciences · 2021Article
- Cellular Interplay as a Consequence of Inflammatory Signals Leading to Liver Fibrosis Development.Cells · 2020Review
- Extracellular ATP Increases Glucose Metabolism in Skeletal Muscle Cells in a P2 Receptor Dependent Manner but Does Not Contribute to Palmitate-Induced Insulin Resistance.Frontiers in physiology · 2020Article
- Oleic and Linoleic Acids Induce the Release of Neutrophil Extracellular TrapsFrontiers in veterinary science · 2020Article
- Purinoceptor expression in hepatocellular virus (HCV)-induced and non-HCV hepatocellular carcinoma: an insight into the proviral role of the P2X4 receptor.Molecular biology reports · 2018Article
- Danger-Associated Molecular Patterns (DAMPs): Molecular Triggers for Sterile Inflammation in the Liver.International journal of molecular sciences · 2018Review
- Genetic ablation of pannexin1 counteracts liver fibrosis in a chemical, but not in a surgical mouse model.Archives of toxicology · 2018Article
- Article
- Protective effect of genetic deletion of pannexin1 in experimental mouse models of acute and chronic liver disease.Biochimica et biophysica acta. Molecular basis of disease · 2018Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocyte lipoapoptosis induced by saturated free fatty acids (FFA) contributes to hepatic inflammation in lipotoxic liver injury, and the cellular mechanisms involved have not been defined. Recent studies have shown that apoptosis in nonhepatic cells stimulates ATP release via activation of pannexin1 (panx1), and extracellular ATP functions as a proinflammatory signal for recruitment and activation of the inflammatory cells. However, it is not known whether lipoapoptosis stimulates ATP release in liver cells. We found that lipoapoptosis induced by saturated FFA stimulated ATP release in liver cells that increased extracellular ATP concentration by more than fivefold above the values observed in healthy cells. This sustained pathophysiological ATP release was not dependent on caspase-3/7 activation. Inhibition of c-Jun NH(2)-terminal kinase (JNK), a key mediator of lipoapoptosis, with SP600125 blocked pathophysiological ATP release in a dose-dependent manner. RT-PCR analysis indicated that panx1 is expressed in hepatocytes and multiple liver cell lines. Notably, inhibition of panx1 expression with short hairpin (sh)RNA inhibited in part pathophysiological ATP release. Moreover, lipoapoptosis stimulated uptake of a membrane impermeable dye YoPro-1 (indicative of panx1 activation), which was inhibited by panx1 shRNA, probenecid, and mefloquine. These results suggest that panx1 contributes to pathophysiological ATP release in lipoapoptosis induced by saturated FFA. Thus panx1 may play an important role in hepatic inflammation by mediating an increase in extracellular ATP concentration in lipotoxic liver injury.
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