title: Downregulation of vitamin C transporter SVCT-2 in doxorubicin-induced cardiomyocyte injury.
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.
authors: Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada.
authors: Ana R
authors: AR
authors: Ludke
authors: Anita K
authors: AK
authors: Sharma
authors: Gauri
authors: G
authors: Akolkar
authors: Gunjan
authors: G
authors: Bajpai
authors: Pawan K
authors: PK
authors: Singal
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D060347:Sodium-Coupled Vitamin C Transporters / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism
chemical_list: C555167:Slc23a2 protein, rat; D060347:Sodium-Coupled Vitamin C Transporters; D004317:Doxorubicin; D001205:Ascorbic Acid