European Journal of Nutrition

, Volume 53, Issue 2, pp 401–412 | Cite as

Liver metabolic/oxidative stress induces hepatic and extrahepatic changes in the expression of the vitamin C transporters SVCT1 and SVCT2

  • Carlos Hierro
  • Maria J. Monte
  • Elisa Lozano
  • Ester Gonzalez-Sanchez
  • Jose J. G. Marin
  • Rocio I. R. Macias
Original Contribution

Abstract

Purpose

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.

Methods and 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.

Keywords

Ascorbic acid Cholestasis Diabetes Obesity 

Supplementary material

394_2013_536_MOESM1_ESM.doc (17 kb)
Supplementary material 1 (DOC 17 kb)
394_2013_536_MOESM2_ESM.doc (66 kb)
Supplementary material 2 (DOC 66 kb)
394_2013_536_MOESM3_ESM.doc (64 kb)
Supplementary material 3 (DOC 64 kb)
394_2013_536_MOESM4_ESM.doc (68 kb)
Supplementary material 4 (DOC 68 kb)
394_2013_536_MOESM5_ESM.tif (10.5 mb)
Liver histology in controls (A), one-week bile duct ligation (BDL) (B, C), streptozotocin-induced diabetes (D), and 12-week-old lean (E) and obese Zucker rats (F). Original magnification: 10x. Hepatocellular degeneration and neutrophil infiltration, asterisks; ductular proliferation, arrow heads; micro- and macrovesicular steatosis; arrows (TIFF 10785 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Carlos Hierro
    • 1
  • Maria J. Monte
    • 1
    • 2
  • Elisa Lozano
    • 1
  • Ester Gonzalez-Sanchez
    • 1
  • Jose J. G. Marin
    • 1
    • 2
  • Rocio I. R. Macias
    • 1
    • 2
  1. 1.Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), Department of Physiology and PharmacologyUniversity of Salamanca, IBSALSalamancaSpain
  2. 2.National Institute for the Study of Liver and Gastrointestinal DiseasesCIBERehdSalamancaSpain

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