Vitamin C inhibits hypoxia-induced damage and apoptotic signaling pathways in cardiomyocytes and ischemic hearts Journal Article
| Authors: | Guaiquil, V. H.; Golde, D. W.; Beckles, D. L.; Mascareno, E. J.; Siddiqui, M. A. Q. |
| Article Title: | Vitamin C inhibits hypoxia-induced damage and apoptotic signaling pathways in cardiomyocytes and ischemic hearts |
| Abstract: | Reactive oxygen species play a central role in myocardial ischemic injury and are a target for therapeutic intervention. Vitamin C is an essential antioxidant yet difficult to deliver in pharmacologic concentration to the myocardium. We found that adult rat cardiomyocytes accumulate vitamin C by transporting dehydroascorbic acid (DHA), the oxidized form of vitamin C, but do not transport ascorbic acid. Loading cells with vitamin C by DHA treatment resulted in resistance to hypoxia- and hypoxia/reoxygenation-induced cell death associated with the quenching of reactive oxygen species. When rats were injected with DHA before coronary occlusion, the ascorbic acid content in the heart was six to eight times higher than in untreated controls and myocardial infarction was reduced by 62%. DHA also provided significant protection when administered intravenously 2 h after coronary occlusion. In cardiomyocytes subjected to hypoxia/reoxygenation, DHA treatment resulted in decreased apoptosis associated with inhibition of Bax expression, caspase-3 activation, and cytochrome c translocation into the cytoplasm. DHA treatment also inhibited Jak2, STAT1, and STAT5 phosphorylation, and increased STAT3 phosphorylation, in hypoxic cardiomyocytes and ischemic myocardial tissue. Our findings suggest that DHA may be useful as a cardioprotectant in ischemic heart disease. © 2004 Elsevier Inc. All rights reserved. |
| Keywords: | signal transduction; controlled study; protein expression; protein phosphorylation; janus kinase 2; nonhuman; protein localization; animal cell; animals; animal tissue; cell death; stat1 protein; stat3 protein; apoptosis; signaling; animal experiment; animal model; caspase 3; enzyme activation; time; hypoxia; injection; ischemia; heart infarction; cell damage; rat; reactive oxygen species; reactive oxygen metabolite; cytoplasm; inhibition kinetics; cell hypoxia; rats; ascorbic acid; rats, sprague-dawley; disease models, animal; stat5 protein; heart muscle cell; drug transport; heart protection; heart; oxidation; dehydroascorbic acid; anoxia; myocardium; heart muscle ischemia; reoxygenation; cytochrome c; protein bax; free radicals; myocardial ischemia; jak/stat; muscle cells; priority journal; article |
| Journal Title: | Free Radical Biology and Medicine |
| Volume: | 37 |
| Issue: | 9 |
| ISSN: | 0891-5849 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2004-11-01 |
| Start Page: | 1419 |
| End Page: | 1429 |
| Language: | English |
| DOI: | 10.1016/j.freeradbiomed.2004.06.041 |
| PROVIDER: | scopus |
| PUBMED: | 15454281 |
| DOI/URL: | |
| Notes: | Free Radic. Biol. Med. -- Cited By (since 1996):42 -- Export Date: 16 June 2014 -- CODEN: FRBME -- Source: Scopus |
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