ArticleThe Journal of clinical investigation2009
Prevention of hepatocarcinogenesis and increased susceptibility to acetaminophen-induced liver failure in transaldolase-deficient mice by N-acetylcysteine.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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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
63 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Liver Disease in Transaldolase Deficiency: Molecular Basis, Genotype-Phenotype Relationships, and Transplantation Outcomes-A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Molecular analysis of individuals with suspected 46,XY differences of sex development in a homogenous and understudied population.Human molecular genetics · 2026Article
- Pathomechanism of Fever-Induced Liver Failure in NBAS Deficiency and Treatment Effect of NAC-Observations In Vitro and In Vivo.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- TALDO1 promotes lipid metabolic reprogramming and immunosuppressive microenvironment remodelling in hepatocellular carcinoma.Clinical and translational medicine · 2026Article
- Transaldolase 1 contributes to pentose phosphate pathway disruption and synaptic dysfunction in Alzheimer's disease.Translational neurodegeneration · 2026Article
- SnRNA-seq and genome-wide CRISPR screening define the complete transcriptional trajectory and functional drivers of podocyte stress.Cellular and molecular life sciences : CMLS · 2026Article
- Transaldolase 1 impacts Parkinson's disease pathogenesis via metabolic reprogramming and autophagy-lysosomal pathway.Acta neuropathologica communications · 2025Article
- Potassium-Hydroxide-Based Extraction of Nicotinamide Adenine Dinucleotides from Biological Samples Offers Accurate Assessment of Intracellular Redox Status.International journal of molecular sciences · 2025Article
- Deacetylation of TALDO1 by HDAC6 promotes glycolysis and nasopharyngeal carcinoma progression through a moonlighting function.Cell death & disease · 2025Article
- Molecular network of metabolic reprogramming and precision diagnosis and treatment of hepatocellular carcinoma.Biomarker research · 2025Review
- Plasma proteomic signature for preoperative prediction of microvascular invasion in HCC.JHEP reports : innovation in hepatology · 2025Article
- Review
- A Rare Cause of Hypergonadotropic Hypogonadism: Transaldolase Deficiency in Two SiblingsJournal of clinical research in pediatric endocrinology · 2025Article
- Gluconolactone restores immune regulation and alleviates skin inflammation in lupus-prone mice and in patients with cutaneous lupus.Science translational medicine · 2025Article
- Oxidative Stress, Inflammation and Altered Glucose Metabolism Contribute to the Retinal Phenotype in the Choroideremia Zebrafish.Antioxidants (Basel, Switzerland) · 2024Article
- Redox Pathogenesis in Rheumatic Diseases.ACR open rheumatology · 2024Review
- mTOR-dependent loss of PON1 secretion and antiphospholipid autoantibody production underlie autoimmunity-mediated cirrhosis in transaldolase deficiency.Journal of autoimmunity · 2023Article
- The NADPH Link between the Renin Angiotensin System and the Antioxidant Mechanisms in Dopaminergic Neurons.Antioxidants (Basel, Switzerland) · 2023Review
- Transaldolase inhibits CD36 expression by modulating glutathione-p38 signaling, exerting protective effects against macrophage foam cell formation.Acta biochimica et biophysica Sinica · 2023Article
- Mitochondria Deregulations in Cancer Offer Several Potential Targets of Therapeutic Interventions.International journal of molecular sciences · 2023Review
3 more citing papers are in PubMed but not listed here.
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15 authors.
Funding
Abstract
Although oxidative stress has been implicated in acute acetaminophen-induced liver failure and in chronic liver cirrhosis and hepatocellular carcinoma (HCC), no common underlying metabolic pathway has been identified. Recent case reports suggest a link between the pentose phosphate pathway (PPP) enzyme transaldolase (TAL; encoded by TALDO1) and liver failure in children. Here, we show that Taldo1-/- and Taldo1+/- mice spontaneously developed HCC, and Taldo1-/- mice had increased susceptibility to acetaminophen-induced liver failure. Oxidative stress in Taldo1-/- livers was characterized by the accumulation of sedoheptulose 7-phosphate, failure to recycle ribose 5-phosphate for the oxidative PPP, depleted NADPH and glutathione levels, and increased production of lipid hydroperoxides. Furthermore, we found evidence of hepatic mitochondrial dysfunction, as indicated by loss of transmembrane potential, diminished mitochondrial mass, and reduced ATP/ADP ratio. Reduced beta-catenin phosphorylation and enhanced c-Jun expression in Taldo1-/- livers reflected adaptation to oxidative stress. Taldo1-/- hepatocytes were resistant to CD95/Fas-mediated apoptosis in vitro and in vivo. Remarkably, lifelong administration of the potent antioxidant N-acetylcysteine (NAC) prevented acetaminophen-induced liver failure, restored Fas-dependent hepatocyte apoptosis, and blocked hepatocarcinogenesis in Taldo1-/- mice. These data reveal a protective role for the TAL-mediated branch of the PPP against hepatocarcinogenesis and identify NAC as a promising treatment for liver disease in TAL deficiency.
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