Hypoxia-reoxygenation-induced mitochondrial damage and apoptosis in human endothelial cells are inhibited by vitamin C Journal Article
| Authors: | Dhar Mascareno, M.; Cárcamo, J. M.; Golde, D. W. |
| Article Title: | Hypoxia-reoxygenation-induced mitochondrial damage and apoptosis in human endothelial cells are inhibited by vitamin C |
| Abstract: | Hypoxia and hypoxia-reperfusion (H-R) play important roles in human pathophysiology because they occur in clinical conditions such as circulatory shock, myocardial ischemia, stroke, and organ transplantation. Reintroduction of oxygen to hypoxic cells during reperfusion causes an increase in generation of reactive oxygen species (ROS), which can alter cell signaling, and cause damage to lipids, proteins, and DNA leading to ischemia-reperfusion injury. Since vitamin C is a potent antioxidant and quenches ROS, we investigated the role of intracellular ascorbic acid (iAA) in endothelial cells undergoing hypoxia-reperfusion. Intracellular AA protected human endothelial cells from H-R-induced apoptosis. Intracellular AA also prevents loss of mitochondrial membrane potential and the release of cytochrome C and activation of caspase-9 and caspase-3 during H-R. Additionally, inhibition of caspase-9 activation prevented H-R-induced apoptosis, suggesting a mitochondrial site of initiation of apoptosis. We found that H-R induced an increase in ROS in endothelial cells that was abrogated in the presence of iAA. Our results indicate that vitamin C prevents hypoxia and H-R-induced damage to human endothelium. © 2005 Elsevier Inc. All rights reserved. |
| Keywords: | controlled study; unclassified drug; human cell; cells, cultured; apoptosis; enzyme inhibition; oxygen; caspase 3; enzyme activation; caspase inhibitor; caspases; hypoxia; endothelium cell; endothelial cells; drug accumulation; drug uptake; umbilical veins; prophylaxis; reactive oxygen species; reactive oxygen metabolite; glucose; caspase 9; cell hypoxia; antioxidant; antioxidants; ascorbic acid; endothelium; cell level; mitochondrial membrane; mitochondria; cell protection; enzyme release; coronary vessels; mitochondrion; dehydroascorbic acid; reoxygenation; cytochrome c; cytochromes c; reperfusion injury; disorders of mitochondrial functions; free radicals; cytochalasin b; membrane potentials; deoxyglucose; benzyloxycarbonylleucylglutamylhistidylaspartyl fluoromethyl ketone; cell membrane potential; monosaccharide transport proteins; hypoxia-reoxygenation; caspase 3 inhibitor; cytochalasin e |
| Journal Title: | Free Radical Biology and Medicine |
| Volume: | 38 |
| Issue: | 10 |
| ISSN: | 0891-5849 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2005-05-15 |
| Start Page: | 1311 |
| End Page: | 1322 |
| Language: | English |
| DOI: | 10.1016/j.freeradbiomed.2005.01.017 |
| PUBMED: | 15855049 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 51" - "Export Date: 24 October 2012" - "CODEN: FRBME" - "Source: Scopus" |
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