Translational control of the ascorbic acid transporter SVCT2 in human platelets.
Reactive oxygen species (ROS) and redox state have emerged as physiological mediators, controlling blood coagulation and thrombosis. The redox balance is obviously linked to the presence of antioxidants; in particular, vitamin C appears to be a key modulator of platelet oxidative state, since these cells physiologically accumulate ascorbic acid and, moreover, platelet ascorbate plays a role during aggregation. Here, we showed that platelets could compensate for fluctuations in ascorbate levels by modulating the expression of the Na+-dependent transporter SVCT2. Furthermore, the use of anucleated cells demonstrated, for the first time, that SVCT2 expression could be regulated at the translational level. The control of ascorbic acid uptake, through regulation of its carrier, was not only related to substrate availability, but it also occurred during platelet activation, which was accompanied by vitamin C deprivation and alteration in the redox state. Finally, we showed that changes in intracellular ascorbic acid content had physiological relevance, since they modulate the surface sulfhydryl content and the thrombus viscoelastic properties. Beside its role during aggregation, vitamin C may also have important effects during postaggregatory events.
Savini
Isabella
I
Department of Experimental Medicine & Biochemical Sciences, University of Rome Tor Vergata, Via Montpellier 1, 00133 Roma, Italy.
Catani
M Valeria
MV
Arnone
Rosaria
R
Rossi
Antonello
A
Frega
Gianluca
G
Del Principe
Domenico
D
Avigliano
Luciana
L
D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics* / Q000378:metabolism; D010084:Oxidation-Reduction; D014176:Protein Biosynthesis / Q000187:drug effects; D060347:Sodium-Coupled Vitamin C Transporters; D013438:Sulfhydryl Compounds / Q000032:analysis / Q000378:metabolism; D027981:Symporters / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects
D029363:Organic Anion Transporters, Sodium-Dependent; C555163:SLC23A2 protein, human; D060347:Sodium-Coupled Vitamin C Transporters; D013438:Sulfhydryl Compounds; D027981:Symporters; D001205:Ascorbic Acid