title: Chronic liver disease is triggered by taurine transporter knockout in the mouse.
abstract: Taurine is an abundant organic osmolyte with antioxidant and immunomodulatory properties. Its role in the pathogenesis of chronic liver disease is unknown. The liver phenotype was studied in taurine transporter knockout (taut-/-) mice. Hepatic taurine levels were ~21, 15 and 6 mumol/g liver wet weight in adult wild-type, heterozygous (taut+/-) and homozygous (taut-/-) mice, respectively. Immunoelectronmicroscopy revealed an almost complete depletion of taurine in Kupffer and sinusoidal endothelial cells, but not in parenchymal cells of (taut-/-) mice. Compared with wild-type mice, (taut-/-) and (taut+/-) mice developed moderate unspecific hepatitis and liver fibrosis with increased frequency of neoplastic lesions beyond 1 year of age. Liver disease in (taut-/-) mice was characterized by hepatocyte apoptosis, activation of the CD95 system, elevated plasma TNF-alpha levels, hepatic stellate cell and oval cell proliferation, and severe mitochondrial abnormalities in liver parenchymal cells. Mitochondrial dysfunction was suggested by a significantly lower respiratory control ratio in isolated mitochondria from (taut-/-) mice. Taut knockout had no effect on taurine-conjugated bile acids in bile; however, the relative amount of cholate-conjugates acid was decreased at the expense of 7-keto-cholate-conjugates. In conclusion, taurine deficiency due to defective taurine transport triggers chronic liver disease, which may involve mitochondrial dysfunction.
authors.affiliation: Clinic for Gastroenterology, Hepatology, and Infectiology, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Warskulat
authors.forename: Elena
authors.initials: E
authors.lastname: Borsch
authors.forename: Roland
authors.initials: R
authors.lastname: Reinehr
authors.forename: Birgit
authors.initials: B
authors.lastname: Heller-Stilb
authors.forename: Irmhild
authors.initials: I
authors.lastname: Mönnighoff
authors.forename: Darius
authors.initials: D
authors.lastname: Buchczyk
authors.forename: Markus
authors.initials: M
authors.lastname: Donner
authors.forename: Ulrich
authors.initials: U
authors.lastname: Flögel
authors.forename: Günther
authors.initials: G
authors.lastname: Kappert
authors.forename: Sibylle
authors.initials: S
authors.lastname: Soboll
authors.forename: Sandra
authors.initials: S
authors.lastname: Beer
authors.forename: Klaus
authors.initials: K
authors.lastname: Pfeffer
authors.forename: Hanns-Ulrich
authors.initials: HU
authors.lastname: Marschall
authors.forename: Marcus
authors.initials: M
authors.lastname: Gabrielsen
authors.forename: Mahmood
authors.initials: M
authors.lastname: Amiry-Moghaddam
authors.forename: Ole Petter
authors.initials: OP
authors.lastname: Ottersen
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Dienes
authors.forename: Dieter
authors.initials: D
authors.lastname: Häussinger
mesh_terms: D000818:Animals; D017209:Apoptosis; D001647:Bile Acids and Salts / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D042783:Endothelial Cells / Q000737:chemistry / Q000473:pathology; D005260:Female; D005838:Genotype; D006505:Hepatitis / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D022781:Hepatocytes / Q000737:chemistry / Q000473:pathology; D007728:Kupffer Cells / Q000737:chemistry / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D026901:Membrane Transport Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008930:Mitochondria, Liver / Q000648:ultrastructure; D018384:Oxidative Stress; D010587:Phagocytosis; D013654:Taurine / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D019014:fas Receptor / Q000378:metabolism; D000099247:Taurine Transporters
chemical_list: D001647:Bile Acids and Salts; D016207:Cytokines; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D013654:Taurine; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D000099247:Taurine Transporters