ArticleThe Journal of cell biology2011
Energy determinants GAPDH and NDPK act as genetic modifiers for hepatocyte inclusion formation.
Article in The Journal of cell biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 36 citations in OpenAlex.
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- Esrra regulates Rplp1-mediated translation of lysosome proteins suppressed in metabolic dysfunction-associated steatohepatitis and reversed by alternate day fasting.Molecular metabolism · 2024Article
- Nucleoside diphosphate kinases 1 and 2 regulate a protective liver response to a high-fat diet.Science advances · 2023Article
- Acitretin mitigates uroporphyrin-induced bone defects in congenital erythropoietic porphyria models.Scientific reports · 2021Article
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- Concurrent isolation of hepatic stem cells and hepatocytes from the human liver.In vitro cellular & developmental biology. Animal · 2020Article
- Porphyrin-Induced Protein Oxidation and Aggregation as a Mechanism of Porphyria-Associated Cell Injury.Cellular and molecular gastroenterology and hepatology · 2019Review
- Clusterin and Pycr1 alterations associate with strain and model differences in susceptibility to experimental pancreatitis.Biochemical and biophysical research communications · 2017Article
- Physicochemical properties that control protein aggregation also determine whether a protein is retained or released from necrotic cells.Open biology · 2016Article
- Mouse genetic background contributes to hepatocyte susceptibility to Fas-mediated apoptosis.Molecular biology of the cell · 2016Article
- Ethanol and Acetaminophen Synergistically Induce Hepatic Aggregation and TCH346-Insensitive Nuclear Translocation of GAPDH.PloS one · 2016Article
- Ambient Light Promotes Selective Subcellular Proteotoxicity after Endogenous and Exogenous Porphyrinogenic Stress.The Journal of biological chemistry · 2015Article
- Modulation of cytoskeletal dynamics by mammalian nucleoside diphosphate kinase (NDPK) proteins.Naunyn-Schmiedeberg's archives of pharmacology · 2015Review
- Alternative splicing of human NT5E in cirrhosis and hepatocellular carcinoma produces a negative regulator of ecto-5'-nucleotidase (CD73).Molecular biology of the cell · 2014Article
- Oxidation of an exposed methionine instigates the aggregation of glyceraldehyde-3-phosphate dehydrogenase.The Journal of biological chemistry · 2014Article
- Carbamoyl phosphate synthetase-1 is a rapid turnover biomarker in mouse and human acute liver injury.American journal of physiology. Gastrointestinal and liver physiology · 2014Article
- Mutation of caspase-digestion sites in keratin 18 interferes with filament reorganization, and predisposes to hepatocyte necrosis and loss of membrane integrity.Journal of cell science · 2014Article
- CD73 (ecto-5'-nucleotidase) hepatocyte levels differ across mouse strains and contribute to mallory-denk body formation.Hepatology (Baltimore, Md.) · 2013Article
- Lamin aggregation is an early sensor of porphyria-induced liver injury.Journal of cell science · 2013Article
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8 authors at 4 institutions in 4 countries.
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Abstract
Genetic factors impact liver injury susceptibility and disease progression. Prominent histological features of some chronic human liver diseases are hepatocyte ballooning and Mallory-Denk bodies. In mice, these features are induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) in a strain-dependent manner, with the C57BL and C3H strains showing high and low susceptibility, respectively. To identify modifiers of DDC-induced liver injury, we compared C57BL and C3H mice using proteomic, biochemical, and cell biological tools. DDC elevated reactive oxygen species (ROS) and oxidative stress enzymes preferentially in C57BL livers and isolated hepatocytes. C57BL livers and hepatocytes also manifested significant down-regulation, aggregation, and nuclear translocation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). GAPDH knockdown depleted bioenergetic and antioxidant enzymes and elevated hepatocyte ROS, whereas GAPDH overexpression decreased hepatocyte ROS. On the other hand, C3H livers had higher expression and activity of the energy-generating nucleoside-diphosphate kinase (NDPK), and knockdown of hepatocyte NDPK augmented DDC-induced ROS formation. Consistent with these findings, cirrhotic, but not normal, human livers contained GAPDH aggregates and NDPK complexes. We propose that GAPDH and NDPK are genetic modifiers of murine DDC-induced liver injury and potentially human liver disease.
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