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Essential role of intracellular glutathione in controlling ascorbic acid transporter expression and function in rat hepatocytes and hepatoma cells.
MedLine Citation:
PMID:  22348976     Owner:  NLM     Status:  Publisher    
Although there is in vivo evidence suggesting a role for glutathione in the metabolism and tissue distribution of vitamin C, no connection with the vitamin C transport systems has been reported. We show here that disruption of glutathione metabolism with buthionine-(SR)-sulfoximine (BSO), produced a sustained blockade of ascorbic acid transport in rat hepatocytes and rat hepatoma cells. Rat hepatocytes expressed the Na(+)-coupled ascorbic acid transporter-1 (SVCT1), while hepatoma cells expressed the transporters SVCT1 and SVCT2. BSO-treated rat hepatoma cells showed a two-order of magnitude decrease in SVCT1 and SVCT2 mRNA levels, undetectable SVCT1 and SVCT2 protein expression, and lacked the capacity to transport ascorbic acid, effects that were fully reversible upon glutathione repletion. Interestingly, although SVCT1 mRNA levels remained unchanged in rat hepatocytes made glutathione deficient by in vivo BSO treatment, SVCT1 protein was absent from the plasma membrane and the cells lacked the capacity to transport ascorbic acid. The specificity of the BSO treatment was indicated by the finding that transport of oxidized vitamin C (dehydroascorbic acid) and glucose transporter expression were unaffected by BSO treatment. Moreover, glutathione depletion failed to affect ascorbic acid transport, and SVCT1 and SVCT2 expression in human hepatoma cells. Therefore, our data indicate an essential role for glutathione in controlling vitamin C metabolism in rat hepatocytes and rat hepatoma cells, two cell types capable of synthesizing ascorbic acid, by regulating the expression and subcellular localization of the transporters involved in the acquisition of ascorbic acid from extracellular sources, an effect not observed in human cells incapable of synthesizing ascorbic acid.
Lorena Mardones; Felipe A Zúñiga; Marcelo Villagrán; Kirsty Sotomayor; Pamela Mendoza; David Escobar; Mauricio González; Valeska Ormazabal; Mafalda Maldonado; Gloria Oñate; Constanza Angulo; Ilona I Concha; Alejandro M Reyes; Juan G Cárcamo; Valeria Barra; Juan Carlos Vera; Coralia I Rivas
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-17
Journal Detail:
Title:  Free radical biology & medicine     Volume:  -     ISSN:  1873-4596     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-2-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Inc.
Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Casilla 160C, Concepción, Chile; Departamento de Ciencias Básicas y Morfología, Facultad de Medicina, Universidad Católica de la Santísima Concepción, Alonso de Ribera 2850, Concepción, Chile.
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