Age-related decline of sodium-dependent ascorbic acid transport in isolated rat hepatocytes.
This study investigated whether the age-related decline in hepatic ascorbic acid (AA) levels in rats was due to altered AA uptake. AA concentrations were 68% lower in freshly isolated hepatocytes from old (24-26 months) versus young (3-5 months; p<0.0005) Fischer 344 rats. When incubated with 100 microM AA, cells from old as compared to young rats showed a 66% decline in both the rate of AA transport and the steady state intracellular levels. Sodium-free media significantly reduced AA uptake, suggesting that the sodium-dependent vitamin C transporter (SVCT) was largely responsible for declines in AA transport. Analysis of SVCT messenger RNA (mRNA) levels shows that one isoform of this transport protein, SVCT1, declines 45% with age, with no significant changes in SVCT2 mRNA levels. These results show for the first time that sodium-dependent AA transport declines during the aging process, which may account for much of the loss in tissue AA content.
Michels
Alexander J
AJ
Linus Pauling Institute and Department of Biochemistry and Biophysics, Oregon State University, 571 Weniger Hall, Corvallis, OR 97331, USA.
Joisher
Neha
N
Hagen
Tory M
TM
D000375:Aging / Q000502:physiology*; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism* / Q000493:pharmacokinetics; D001692:Biological Transport / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003683:Dehydroascorbic Acid / Q000378:metabolism; D003847:Deoxyglucose / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000502:physiology*; D016014:Linear Models; D008297:Male; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012964:Sodium / Q000378:metabolism*; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters / Q000235:genetics / Q000378:metabolism
D029363:Organic Anion Transporters, Sodium-Dependent; C555166:Slc23a1 protein, rat; C555167:Slc23a2 protein, rat; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D003847:Deoxyglucose; D012964:Sodium; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid