Redox regulation of vitamin C transporter SVCT2 in C2C12 myotubes.
We have previously demonstrated that skeletal muscle cells possess efficient systems for vitamin C accumulation; in particular, the SVCT2 transporter for ascorbic acid uptake seems to play a crucial role. In this study, we investigated the regulatory mechanism(s) accounting for SVCT2 activity in C2C12 myotubes. We found that transcription of the SVCT2 gene could be positively or negatively modulated by the presence of oxidant (H(2)O(2)) or antioxidant (lipoate) compounds, respectively. This redox-mediated regulation of SVCT2 expression seemed to be achieved via AP-1 and NF-kappaB signaling. Our findings could be relevant in skeletal muscle, where reactive oxygen species, naturally produced during physical exercise, can induce muscle damage. Thus, the redox-sensitive SVCT2 expression can be placed among the adaptive responses induced by contractile activity.
Savini
Isabella
I
Department of Experimental Medicine & Biochemical Sciences, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
Rossi
Antonello
A
Catani
Maria Valeria
MV
Ceci
Roberta
R
Avigliano
Luciana
L
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism
D000975:Antioxidants; D016328:NF-kappa B; D029363:Organic Anion Transporters, Sodium-Dependent; C555165:Slc23a2 protein, mouse; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D018808:Transcription Factor AP-1; D004247:DNA; D006861:Hydrogen Peroxide; D001205:Ascorbic Acid