Vitamin C homeostasis in skeletal muscle cells.
In skeletal muscle, vitamin C not only enhances carnitine biosynthesis but also protects cells against ROS generation induced by physical exercise. The ability to take up both ascorbic and dehydroascorbic acid from the extracellular environment, together with the ability to recycle the intracellular vitamin, maintains high cellular stores of ascorbate. In this study, we examined vitamin C transport and recycling, by using the mouse C2C12 and rat L6C5 muscle cell lines, which exhibit different sensitivity to oxidative stress and GSH metabolism. We found that: (1) both cell lines express SVCT2, whereas SVCT1 is expressed at very low levels only in proliferating L6C5 cells; furthermore L6C5 myoblasts are more efficient in ascorbic acid transport than C2C12 myoblasts; (2) C2C12 cells are more efficient in dehydroascorbic acid transport and ascorbyl free radical/dehydroascorbic acid reduction; (3) differentiation is paralleled by decreased ascorbic acid and dehydroascorbic acid transport and reduction and increased ascorbyl free radical reduction; (4) differentiated cells are more responsive to oxidative stress induced by glutathione depletion; indeed, myotubes showed increased SVCT2 expression and thioredoxin reductase-mediated dehydroascorbic acid reduction. From our data, SVCT2 and NADPH-thioredoxin-dependent DHA reduction appears to belong to an inducible system activated in response to oxidative stress.
Savini
Isabella
I
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
Catani
Maria Valeria
MV
Duranti
Guglielmo
G
Ceci
Roberta
R
Sabatini
Stefania
S
Avigliano
Luciana
L
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D001692:Biological Transport; D002454:Cell Differentiation; D002460:Cell Line; D003683:Dehydroascorbic Acid / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006706:Homeostasis; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D029363:Organic Anion Transporters, Sodium-Dependent / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters / Q000378:metabolism*; D013879:Thioredoxins / Q000378:metabolism
D029363:Organic Anion Transporters, Sodium-Dependent; C555164:Slc23a1 protein, mouse; C555166:Slc23a1 protein, rat; C555165:Slc23a2 protein, mouse; C555167:Slc23a2 protein, rat; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D013879:Thioredoxins; D009249:NADP; D005978:Glutathione; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid