ArticleThe Journal of clinical investigation2004
Acidic sphingomyelinase downregulates the liver-specific methionine adenosyltransferase 1A, contributing to tumor necrosis factor-induced lethal hepatitis.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 67 citations in OpenAlex.
- Ceramides and neuroinflammation as immunometabolic drivers and biomarkers of major depressive disorder, treatment-resistant depression, and suicidal vulnerability.Frontiers in pharmacology · 2026Review
- The relevance of acid sphingomyelinase as a potential target for therapeutic intervention in hepatic disorders: current scenario and anticipated trends.Archives of toxicology · 2023Review
- Assessing potential liver injury induced byPharmaceutical biology · 2022Article
- Lipids in Liver Failure Syndromes: A Focus on Eicosanoids, Specialized Pro-Resolving Lipid Mediators and Lysophospholipids.Frontiers in immunology · 2022Review
- The Role of Methyl Donors of the Methionine Cycle in Gastrointestinal Infection and Inflammation.Healthcare (Basel, Switzerland) · 2021Review
- Metabolomic Signature as a Predictor of Liver Disease Events in Patients With HIV/HCV Coinfection.The Journal of infectious diseases · 2020Article
- Sphingomyelinases and Liver Diseases.Biomolecules · 2020Review
- Acid Sphingomyelinase Inhibition Prevents Development of Sepsis Sequelae in the Murine Liver.Scientific reports · 2017Article
- Article
- Glycosphingolipids and cell death: one aim, many ways.Apoptosis : an international journal on programmed cell death · 2015Review
- ASMase regulates autophagy and lysosomal membrane permeabilization and its inhibition prevents early stage non-alcoholic steatohepatitis.Journal of hepatology · 2014Article
- Copper: toxicological relevance and mechanisms.Archives of toxicology · 2014Review
- Mitochondrial cholesterol accumulation in alcoholic liver disease: Role of ASMase and endoplasmic reticulum stress.Redox biology · 2014Review
- Membrane TNF-alpha-activated programmed necrosis is mediated by Ceramide-induced reactive oxygen species.Journal of molecular signaling · 2013Article
- Mitochondrial glutathione: features, regulation and role in disease.Biochimica et biophysica acta · 2013Review
- Using ASMase knockout mice to model human diseases.Handbook of experimental pharmacology · 2013Review
- S-adenosylmethionine in liver health, injury, and cancer.Physiological reviews · 2012Review
- Cathepsin B overexpression due to acid sphingomyelinase ablation promotes liver fibrosis in Niemann-Pick disease.The Journal of biological chemistry · 2012Article
- Metabolomic profiling to identify predictors of response to vitamin E for non-alcoholic steatohepatitis (NASH).PloS one · 2012Article
- Liquid chromatography-mass spectrometry-based parallel metabolic profiling of human and mouse model serum reveals putative biomarkers associated with the progression of nonalcoholic fatty liver disease.Journal of proteome research · 2010Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
S-adenosyl-L-methionine (SAM) is synthesized by methionine adenosyltransferases (MATs). Ablation of the liver-specific MAT1A gene results in liver neoplasia and sensitivity to oxidant injury. Here we show that acidic sphingomyelinase (ASMase) mediates the downregulation of MAT1A by TNF-alpha. The levels of MAT1A mRNA as well as MAT I/III protein decreased in cultured rat hepatocytes by in situ generation of ceramide from exogenous human placenta ASMase. Hepatocytes lacking the ASMase gene (ASMase-/-) were insensitive to TNF-alpha but were responsive to exogenous ASMase-induced downregulation of MAT1A. In an in vivo model of lethal hepatitis by TNF-alpha, depletion of SAM preceded activation of caspases 8 and 3, massive liver damage, and death of the mice. In contrast, minimal hepatic SAM depletion, caspase activation, and liver damage were seen in ASMase-/- mice. Moreover, therapeutic treatment with SAM abrogated caspase activation and liver injury, thus rescuing ASMase+/+ mice from TNF-alpha-induced lethality. Thus, we have demonstrated a new role for ASMase in TNF-alpha-induced liver failure through downregulation of MAT1A, and maintenance of SAM may be useful in the treatment of acute and chronic liver diseases.
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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.