title: Hepatic expression of sodium-dependent vitamin C transporters: ontogeny, subtissular distribution and effect of chronic liver diseases.
abstract: Ascorbic acid uptake is a key step in determining the overall bioactivity of this vitamin. Expression of Na-dependent vitamin C transporters (SVCT; SLC23A1 and SLC23A2) during long-term oxidative stress occurring in several chronic liver diseases may determine the antioxidant defence in this organ. In patients with hepatocellular cholestasis, primary biliary cirrhosis, haemochromatosis and non-alcoholic steatohepatitis, using real-time RT-PCR, an enhanced hepatic expression of both SLC23A1 and SLC23A2, but not other organic anions transporters, such as OATP1A2, OATP1B1 and OATP1B3, was found. To further investigate these findings, we used secondary biliary cirrhosis induced in rats by long-term biliary obstruction as a model of chronic liver disease accompanied by oxidative stress because of bile acid accumulation. In control rat liver, expression of Slc23a1 was low at birth, increased progressively up to adulthood and decreased in senescence, whereas expression of Slc23a2 did not change significantly after birth. In 8-week-old rats, immunohistochemistry and confocal microscopy studies revealed the expression in hepatocytes and bile duct cells of mainly Slc23a1, whereas both Slc23a1 and Slc23a2 were expressed in endothelial, stellate and Kupffer cells. In adult rats, when obstructive cholestasis was maintained for 8 weeks, a significant up-regulation of Slc23a2 accompanied by a down-regulation of Slc23a1 was found. In sum, there is a selective cell-type distribution of SVCT in the liver tissue, which, in addition to differential control in the expression of both isoforms, may play a role in the ability of different liver cell types to take up vitamin C under physiological and pathological conditions.
authors: Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), University of Salamanca, Salamanca, Spain.
authors: Rocio I R
authors: RI
authors: Macias
authors: Carlos
authors: C
authors: Hierro
authors: Susana Cuesta
authors: SC
authors: de Juan
authors: Felipe
authors: F
authors: Jimenez
authors: Francisco
authors: F
authors: Gonzalez-San Martin
authors: Jose J G
authors: JJ
authors: Marin
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002779:Cholestasis / Q000235:genetics; D002908:Chronic Disease; D005234:Fatty Liver / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006432:Hemochromatosis / Q000235:genetics; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008105:Liver Cirrhosis, Biliary / Q000235:genetics; D008107:Liver Diseases / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060347:Sodium-Coupled Vitamin C Transporters / Q000235:genetics* / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: 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