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Downregulation of vitamin C transporter SVCT-2 in doxorubicin-induced cardiomyocyte injury.
- Source :
-
American journal of physiology. Cell physiology [Am J Physiol Cell Physiol] 2012 Sep 15; Vol. 303 (6), pp. C645-53. Date of Electronic Publication: 2012 Jul 03. - Publication Year :
- 2012
-
Abstract
- Vitamin C (Vit C) has been shown to be protective against doxorubicin (Dox)-induced cardiotoxicity. However, Vit C uptake into cardiomyocytes is poorly understood. Furthermore, whether the antioxidant enzyme reserve is enhanced by Vit C is also not known. The present study investigated an influence of Dox on Vit C transporters, expression of endogenous antioxidant reserve as well as enzymes, oxidative stress, and apoptosis in isolated cardiomyocytes. Cardiomyocytes isolated from adult Sprague-Dawley rats were exposed to control (culture medium 199 alone), Dox (10 μM), Vit C (25 μM), and Vit C + Dox for 24 h. Vit C transporter expression and localization, oxidative stress, antioxidant enzymes, and apoptosis were studied. Expression and localization of sodium-dependent vitamin C transporter-2 (SVCT-2) in the sarcolemma was reduced by Dox, but Vit C supplementation was able to blunt this change. There was a decrease in the expression of antioxidant enzymes glutathione peroxidase (GPx), catalase, and Cu/Zn superoxide dismutase (SOD) due to Dox, but only GPx expression was completely prevented and Cu/Zn SOD was partially rescued by Vit C. Dox-induced decrease in antioxidant reserve and increase in oxidative stress were partially mitigated by Vit C. Dox-induced apoptosis was ameliorated by Vit C. It is suggested that cardioprotection offered by Vit C in Dox-induced cardiomyopathy may involve an upregulation of SVCT-2 transporter followed by a reduction in oxidative stress as well as blunting of cardiomyocyte injury.
- Subjects :
- Animals
Ascorbic Acid metabolism
Cells, Cultured
Down-Regulation drug effects
Doxorubicin antagonists & inhibitors
Male
Myocytes, Cardiac drug effects
Oxidative Stress drug effects
Oxidative Stress physiology
Rats
Rats, Sprague-Dawley
Sodium-Coupled Vitamin C Transporters biosynthesis
Sodium-Coupled Vitamin C Transporters metabolism
Ascorbic Acid pharmacology
Down-Regulation physiology
Doxorubicin toxicity
Myocytes, Cardiac metabolism
Myocytes, Cardiac pathology
Sodium-Coupled Vitamin C Transporters antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1563
- Volume :
- 303
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Cell physiology
- Publication Type :
- Academic Journal
- Accession number :
- 22763122
- Full Text :
- https://doi.org/10.1152/ajpcell.00186.2012