Ascorbic acid depletion enhances expression of the sodium-dependent vitamin C transporters, SVCT1 and SVCT2, and uptake of ascorbic acid in livers of SMP30/GNL knockout mice.
In this study, we examined whether ascorbic acid (AA) and dehydroascorbic acid (DHA), the oxidized form of AA, levels in tissues regulate the AA transporters, sodium-dependent vitamin C transporters (SVCT) 1 and SVCT2 and DHA transporters, glucose transporter (GLUT) 1, GLUT3, GLUT4 mRNA by using senescence marker protein-30 (SMP30)/gluconolactonase (GNL) knockout (KO) mice. These mice are incapable of synthesizing AA in vivo. AA depletion enhanced SVCT1 and SVCT2 mRNA expression in the liver and SVCT1 and GLUT4 mRNA expression in the small intestine, but not in the cerebrum or kidney. Next, we examined the actual impact of AA uptake by using primary cultured hepatocytes from SMP30/GNL KO mice. In the AA-depleted hepatocytes from SMP30/GNL KO mice, AA uptake was significantly greater than in matched cultures from wild-type mice. These results strongly affirm that intracellular AA is an important regulator of SVCT1 and SVCT2 expression in the liver.
Amano
Akiko
A
Cellular Genetics, Graduate School of Science and Engineering, Tokyo Metropolitan University, Tokyo 192-0397, Japan.
Aigaki
Toshiro
T
Maruyama
Naoki
N
Ishigami
Akihito
A
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D001692:Biological Transport; D001835:Body Weight; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D002265:Carboxylic Ester Hydrolases / Q000172:deficiency / Q000235:genetics*; D003683:Dehydroascorbic Acid / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics; D022781:Hepatocytes / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters / Q000235:genetics* / Q000378:metabolism
D002135:Calcium-Binding Proteins; D051246:Glucose Transport Proteins, Facilitative; D047908:Intracellular Signaling Peptides and Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger; C513324:Rgn protein, mouse; C555164:Slc23a1 protein, mouse; C555165:Slc23a2 protein, mouse; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D002265:Carboxylic Ester Hydrolases; C020579:gluconolactonase; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid