title: Liver metabolic/oxidative stress induces hepatic and extrahepatic changes in the expression of the vitamin C transporters SVCT1 and SVCT2.
abstract: OBJECTIVE
  Owing to its ability to inactivate harmful radicals, vitamin C plays a key role in antioxidant defense. The bioavailability of this vitamin depends upon the nutritional intake and its uptake by cells, mainly through the sodium-dependent transporters SVCT1/Svct1 and SVCT2/Svct2 (human/rat). Here, we investigated the effect of liver metabolic/oxidative stress on the expression of these transporters in extrahepatic tissues.
  
  
  RESULTS
  In Zucker rats, used here as a model of liver steatosis, Svct1-2 mRNA levels were similar in obese and lean animals, except for lung tissue, where Svct2 was up-regulated. Diabetes mellitus, developed by streptozotocin administration, was accompanied by a down-regulation of Svct1 in liver and kidney, together with a down-regulation of Svct2 in kidney and brain. Complete obstructive cholestasis due to bile duct ligation for 1 week induced a significant down-regulation of both Svct1 and Svct2 in ileum, whereas Svct2 was up-regulated in liver, and no significant changes in the expression of either transporter were found in kidney, brain or lung. In rat hepatoma Can-10 cells, bile acids, but not the FXR agonist GW4064, induced an up-regulation of Svct1 and Svct2. In human hepatoma Alexander cells transfected with FXR/RXRα/OATP1B1, neither GW4064 nor unconjugated or glycine-/taurine-conjugated major bile acids were able to up-regulate either SVCT1 or SVCT2.
  
  
  CONCLUSIONS
  Pathological circumstances characterized by the presence of metabolic/oxidative stress in the liver induce different responses in the expression of ascorbic acid transporters in intrahepatic and extrahepatic tissues, which may affect the overall bioavailability and cellular uptake of this vitamin.
authors.affiliation: Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), Department of Physiology and Pharmacology, University of Salamanca, IBSAL, Campus Miguel de Unamuno E.I.D. B-17, 37007, Salamanca, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Hierro
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Monte
authors.forename: Elisa
authors.initials: E
authors.lastname: Lozano
authors.forename: Ester
authors.initials: E
authors.lastname: Gonzalez-Sanchez
authors.forename: Jose J G
authors.initials: JJ
authors.lastname: Marin
authors.forename: Rocio I R
authors.initials: RI
authors.lastname: Macias
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000493:pharmacokinetics / Q000494:pharmacology; D001647:Bile Acids and Salts / Q000494:pharmacology; D001682:Biological Availability; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D045744:Cell Line, Tumor; D002779:Cholestasis / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000150:complications; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011924:Rats, Zucker; D060347:Sodium-Coupled Vitamin C Transporters / Q000235:genetics*; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D001647:Bile Acids and Salts; D012333:RNA, Messenger; C555162:SLC23A1 protein, human; C555163:SLC23A2 protein, human; C555166:Slc23a1 protein, rat; C555167:Slc23a2 protein, rat; D060347:Sodium-Coupled Vitamin C Transporters; D001205:Ascorbic Acid