ArticleThe Journal of biological chemistry2003
Chronic ethanol exposure increases the binding of HuR to the TNFalpha 3'-untranslated region in macrophages.
Article in The Journal of biological chemistry, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 54 citations in OpenAlex.
- Biological function of RNA-binding proteins in myocardial infarction: a potential emerging therapeutic limelight.Cell & bioscience · 2025Review
- Hepatic Knockdown of Splicing Regulator Slu7 Ameliorates Inflammation and Attenuates Liver Injury in Ethanol-Fed Mice.The American journal of pathology · 2018Article
- Hyaluronic acid 35 normalizes TLR4 signaling in Kupffer cells from ethanol-fed rats via regulation of microRNA291b and its target Tollip.Scientific reports · 2017Article
- MicroRNA 181b-3p and its target importin α5 regulate toll-like receptor 4 signaling in Kupffer cells and liver injury in mice in response to ethanol.Hepatology (Baltimore, Md.) · 2017Article
- Guardian of Genetic Messenger-RNA-Binding Proteins.Biomolecules · 2016Review
- Role of microRNAs in Alcohol-Induced Multi-Organ Injury.Biomolecules · 2015Review
- RNA-stabilizing proteins as molecular targets in cardiovascular pathologies.Trends in cardiovascular medicine · 2015Review
- Identifying Novel Targets for Treatment of Liver Fibrosis: What Can We Learn from Injured Tissues which Heal Without a Scar?Current drug targets · 2015Review
- The C-terminal RNA binding motif of HuR is a multi-functional domain leading to HuR oligomerization and binding to U-rich RNA targets.RNA biology · 2014Article
- Posttranscriptional gene regulation of IL-17 by the RNA-binding protein HuR is required for initiation of experimental autoimmune encephalomyelitis.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Multiple functions of the RNA-binding protein HuR in cancer progression, treatment responses and prognosis.International journal of molecular sciences · 2013Review
- Concurrent binding and modifications of AUF1 and HuR mediate the pH-responsive stabilization of phosphoenolpyruvate carboxykinase mRNA in kidney cells.American journal of physiology. Renal physiology · 2012Article
- MicroRNA-217 promotes ethanol-induced fat accumulation in hepatocytes by down-regulating SIRT1.The Journal of biological chemistry · 2012Article
- MicroRNA Signature in Alcoholic Liver Disease.International journal of hepatology · 2012Article
- Role of AUF1 and HuR in the pH-responsive stabilization of phosphoenolpyruvate carboxykinase mRNA in LLC-PK₁-F⁺ cells.American journal of physiology. Renal physiology · 2011Article
- Up-regulation of microRNA-155 in macrophages contributes to increased tumor necrosis factor {alpha} (TNF{alpha}) production via increased mRNA half-life in alcoholic liver disease.The Journal of biological chemistry · 2011Article
- Thy-1 mRNA destabilization by norepinephrine a 3' UTR cAMP responsive decay element and involves RNA binding proteins.Brain, behavior, and immunity · 2010Article
- Promotion of exon 6 inclusion in HuD pre-mRNA by Hu protein family members.Nucleic acids research · 2010Article
- Chemical inhibitors destabilize HuR binding to the AU-rich element of TNF-alpha mRNA.Experimental & molecular medicine · 2009Article
- An early complement-dependent and TLR-4-independent phase in the pathogenesis of ethanol-induced liver injury in mice.Hepatology (Baltimore, Md.) · 2009Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Tumor necrosis factor alpha (TNFalpha) expression is a key mediator of ethanol-induced liver disease. Increased lipopolysaccharide (LPS)-stimulated TNFalpha expression in macrophages after chronic ethanol feeding is associated with a stabilization of TNFalpha mRNA (Kishore, R., McMullen, M. R., and Nagy, L. E. (2001) J. Biol. Chem. 276, 41930-41937). Here we show that the 3'-UTR of murine TNFalpha mRNA was sufficient to mediate increased LPS-stimulated expression of a luciferase reporter in RAW 264.7 macrophages after chronic ethanol exposure. Further, we show that HuR, a nuclear/cytoplasmic shuttling protein, which binds to TNFalpha mRNA, is required for increased expression of TNFalpha after chronic ethanol. In Kupffer cells, HuR was primarily localized to the nucleus and then translocated to the cytosol in response to LPS in both pair- and ethanol-fed rats. After chronic ethanol feeding, HuR quantity in the cytosol was greater, both at baseline and in response to LPS, compared with pair-fed controls. Using RNA gel shift assays, we found that LPS treatment increased HuR binding to the 65-nucleotide A + U-rich element of the TNFalpha 3'-UTR by 2-fold over baseline in Kupffer cells from pair-fed rats. After chronic ethanol feeding, HuR binding to the TNFalpha A + U-rich element was increased by more than 5-fold at baseline and in response to LPS, compared with pair-fed controls. Down-regulation of HuR expression by RNA interference prevented the chronic ethanol-induced increase in expression of luciferase reporters containing the TNFalpha 3'-UTR. Taken together, these data demonstrate that increased binding of HuR to the TNFalpha 3'-UTR contributes to increased LPS-stimulated TNFalpha expression in macrophages after chronic ethanol exposure.
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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.