Dexamethasone induces sodium-dependant vitamin C transporter in a mouse osteoblastic cell line MC3T3-E1.
The regulation of intracellular ascorbic acid (AsA) levels may be under the control of an AsA-specific membrane transporter. The present study investigates AsA uptake and expression of Na-dependent vitamin C transporter (SVCT) mRNA in the mouse osteoblastic cell line, MC3T3-E1. Among eight compounds tested, dexamethasone (Dex) all-trans retinoic acid, transforming growth factor beta, prostaglandin E2 and transferrin significantly and respectively) stimulated the update of AsA into MC3T3-E1 cells. Among these five, Dex was the most active, inducing mSVCT2 mRNA and the uptake of AsA in a time- and concentration-dependant manner. Dex did not induce mSVCT1 mRNA. These results suggest that the Dex-induced stimulation of AsA incorporation into osteoblastic cells is mediated by the induction of mSVCT2. Since Dex reduced alkaline phosphatase activity in MC3T3-E1 cells in our culture conditions, Dex-induced stimulation of AsA incorporation might not be the result of differentiation. Hormone-regulated changes of SVCT expression may have an important role in cell functions.
Fujita
I
I
Department of Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6, Yamada-oka, Suita, Osaka 565-0871, Japan.
Hirano
J
J
Itoh
N
N
Nakanishi
T
T
Tanaka
K
K
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000494:pharmacology*; D051379:Mice; D029363:Organic Anion Transporters, Sodium-Dependent; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis*; D060347:Sodium-Coupled Vitamin C Transporters; D013268:Stimulation, Chemical; D027981:Symporters; D014407:Tumor Cells, Cultured / Q000187:drug effects
D002352:Carrier Proteins; D005938:Glucocorticoids; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D003907:Dexamethasone; D000469:Alkaline Phosphatase; D001205:Ascorbic Acid