PloS one, 2014-02, Vol.9 (2), p.e87871
2014
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- Autor(en) / Beteiligte
- Titel
- Caveolin-1 is a critical determinant of autophagy, metabolic switching, and oxidative stress in vascular endothelium
- Ist Teil von
- PloS one, 2014-02, Vol.9 (2), p.e87871
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2014
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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 H₂O₂. 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0087871Titel-ID: cdi_plos_journals_1494057801
- Format
- –
- Schlagworte
- Abnormalities, Animals, Aorta - metabolism, Aorta - pathology, Autophagy, Bioindicators, Biology, Biomarkers, Cancer, Cardiovascular diseases, Catalase - metabolism, Cattle, Caveolin, Caveolin 1 - antagonists & inhibitors, Caveolin 1 - physiology, Caveolin-1, Cell culture, Cell death, Cells, Cultured, Endothelial cells, Endothelium, Endothelium, Vascular - metabolism, Endothelium, Vascular - pathology, Experiments, Fatty acids, Fibroblasts, Glucose, Glutathione - metabolism, Glycolysis, Heart diseases, Homeostasis, Hospitals, Hydrogen peroxide, Hydrogen Peroxide - metabolism, Hypertension, Insulin resistance, Intermediates, Kinases, Laboratories, Life sciences, Lysates, Medical schools, Medicine, Metabolism, Metabolome, Metabolomics, Mice, Mice, Knockout, Mitochondria, Mitochondria - metabolism, Mitochondria - pathology, Molecular modelling, Nitric oxide, Oxidative Stress, Phagocytosis, Physiology, Proteins, Reactive Oxygen Species - metabolism, RNA, Small Interfering - genetics, Rodents, Scaffolding, Signal Transduction, Signaling, siRNA, Switching