ArticleFree radical biology & medicine2014
Molecular mechanisms of lipopolysaccharide-mediated inhibition of glutathione synthesis in mice.
Article in Free radical biology & medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- Fenofibrate Mitigates Acute Lung Injury in a Rat Model of Feces-Induced Peritonitis.International journal of molecular sciences · 2026Article
- Ferroptosis suppressor protein 1-mediated ferroptosis suppression in sepsis: non-canonical antioxidant pathways, inflammatory regulation, and therapeutic perspectives.Frontiers in immunology · 2026Review
- Lycopene Mitigates Rat Liver Damage Induced by Lipopolysaccharide via Mechanisms Involving Oxidative Stress, Inflammation, and Apoptosis.Current issues in molecular biology · 2025Article
- Novel Hybrid Peptide DEFB126 (1-39)-TP5 Inhibits LPS-Induced Inflammatory Responses and Oxidative Stress by Neutralizing LPS and Blocking the TLR4/MD2-NFκB Signaling Axis.Antioxidants (Basel, Switzerland) · 2025Article
- Skatole Alleviates Osteoarthritis by Reprogramming Macrophage Polarization and Protecting Chondrocytes.Research (Washington, D.C.) · 2025Article
- 2,4'-Dihydroxybenzophenone: A Promising Anti-Inflammatory Agent Targeting Toll-like Receptor 4/Myeloid Differentiation Factor 2-Mediated Mitochondrial Reactive Oxygen Species Production during Lipopolysaccharide-Induced Systemic Inflammation.ACS pharmacology & translational science · 2024Article
- Advances in Understanding the Role of NRF2 in Liver Pathophysiology and Its Relationship with Hepatic-Specific Cyclooxygenase-2 Expression.Antioxidants (Basel, Switzerland) · 2023Review
- Nrf2-A Molecular Target for Sepsis Patients in Critical Care.Biomolecules · 2020Review
- Down regulation of glutathione and glutamate cysteine ligase in the inflammatory response of macrophages.Free radical biology & medicine · 2020Article
- Responsive Expression of MafF toDisease markers · 2020Article
- SUMOylation and phosphorylation cross-talk in hepatocellular carcinoma.Translational gastroenterology and hepatology · 2018Review
- Temporal changes in glutathione biosynthesis during the lipopolysaccharide-induced inflammatory response of THP-1 macrophages.Free radical biology & medicine · 2017Article
- MicroRNA-mediated regulation of glutathione and methionine metabolism and its relevance for liver disease.Free radical biology & medicine · 2016Review
- Metformin exerts glucose-lowering action in high-fat fed mice via attenuating endotoxemia and enhancing insulin signaling.Acta pharmacologica Sinica · 2016Article
- Aberrant post-translational protein modifications in the pathogenesis of alcohol-induced liver injury.World journal of gastroenterology · 2016Review
- Nuclear Factor-Erythroid-2-Related Factor 2 in Aging and Lung Fibrosis.The American journal of pathology · 2016Review
- Oxidative stress response and Nrf2 signaling in aging.Free radical biology & medicine · 2015Review
- Activation of a novel c-Myc-miR27-prohibitin 1 circuitry in cholestatic liver injury inhibits glutathione synthesis in mice.Antioxidants & redox signaling · 2015Article
- Role of Nrf2 in chronic liver disease.World journal of gastroenterology · 2014Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Endotoxemia correlates with the degree of liver failure and may participate in worsening of liver diseases. Lipopolysaccharide (LPS; synonymous with endotoxin) treatment in mice lowered the hepatic glutathione (GSH) level, which in turn is a variable that determines susceptibility to LPS-induced injury. We previously showed that LPS treatment in mice lowered hepatic expression of the rate-limiting enzyme in GSH synthesis, glutamate-cysteine ligase (GCL). The aim of our current work was to determine the molecular mechanism(s) responsible for these changes. Studies were done using RAW cells (murine macrophages), in vivo LPS-treated mice, and mouse hepatocytes. We found that LPS treatment lowered GCL catalytic and modifier (Gclc and Gclm) subunit expression at the transcriptional level, which was unrelated to alterations in nitric oxide production or induction of NF-κB/p65 subunit. The key mechanism was a decrease in sumoylation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and MafG, which is required for their heterodimerization and subsequent binding and trans-activation of the antioxidant-response element (ARE) present in the promoter region of these genes that is essential for their expression. LPS treatment lowered markedly the expression of ubiquitin-conjugating enzyme 9 (Ubc9), which is required for sumoylation. Similar findings also occurred in liver after in vivo LPS treatment and in LPS-treated mouse hepatocytes. Overexpression of Ubc9 protected against LPS-mediated inhibition of Gclc and Gclm expression in RAW cells and hepatocytes. In conclusion, LPS-mediated lowering of GCL expression in hepatocytes and macrophages is due to lowering of sumoylation of Nrf2 and MafG, leading to reduced heterodimerization, binding, and trans-activation of ARE.
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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.