| First Author | Shiroto T | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 2 | Pages | e87871 |
| PubMed ID | 24498385 | Mgi Jnum | J:212844 |
| Mgi Id | MGI:5582345 | Doi | 10.1371/journal.pone.0087871 |
| Citation | Shiroto T, et al. (2014) Caveolin-1 is a critical determinant of autophagy, metabolic switching, and oxidative stress in vascular endothelium. PLoS One 9(2):e87871 |
| abstractText | Caveolin-1 is a scaffolding/regulatory protein that interacts with diverse signaling molecules. Caveolin-1(null) mice have marked metabolic abnormalities, yet the underlying molecular mechanisms are incompletely understood. We found the redox stress plasma biomarker plasma 8-isoprostane was elevated in caveolin-1(null) mice, and discovered that siRNA-mediated caveolin-1 knockdown in endothelial cells promoted significant increases in intracellular H(2)O(2). Mitochondrial ROS production was increased in endothelial cells after caveolin-1 knockdown; 2-deoxy-D-glucose attenuated this increase, implicating caveolin-1 in control of glycolytic pathways. We performed unbiased metabolomic characterizations of endothelial cell lysates following caveolin-1 knockdown, and discovered strikingly increased levels (up to 30-fold) of cellular dipeptides, consistent with autophagy activation. Metabolomic analyses revealed that caveolin-1 knockdown led to a decrease in glycolytic intermediates, accompanied by an increase in fatty acids, suggesting a metabolic switch. Taken together, these results establish that caveolin-1 plays a central role in regulation of oxidative stress, metabolic switching, and autophagy in the endothelium, and may represent a critical target in cardiovascular diseases. |
