Caveolin-1 regulates lipid droplet metabolism in endothelial cells via autocrine prostacyclin–stimulated, cAMP-mediated lipolysis
| Autor: | Andrew Kuo, William C. Sessa, Kui Yang, Richard W. Gross, Monica Y. Lee |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Lipolysis Blotting Western Caveolin 1 Caveola assembly Prostaglandin Prostacyclin Biochemistry Mass Spectrometry Cell Line Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Lipid droplet Cyclic AMP medicine Animals Phosphorylation Autocrine signalling Molecular Biology Cells Cultured Endothelial Cells Lipid metabolism Cell Biology Lipid Metabolism Epoprostenol Mice Mutant Strains Cell biology 030104 developmental biology chemistry 030220 oncology & carcinogenesis cardiovascular system medicine.drug |
| Zdroj: | Journal of Biological Chemistry. 293:973-983 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.ra117.000980 |
| Popis: | Lipid droplets (LD) are dynamic organelles involved in intracellular lipid metabolism in almost all eukaryotic cells, and LD-associated proteins tightly regulate their dynamics. One LD coat protein is caveolin-1 (Cav-1), an essential component for caveola assembly in highly differentiated cells, including adipocytes, smooth muscle cells, and endothelial cells (EC). However, the role of Cav-1 in LD dynamics is unclear. Here we report that EC lacking Cav-1 exhibit impaired LD formation. The decreased LD formation is due to enhanced lipolysis and not caused by reduced triglyceride synthesis or fatty acid uptake. Mechanistically, the absence of Cav-1 increased cAMP/PKA signaling in EC, as indicated by elevated phosphorylation of hormone-sensitive lipase and increased lipolysis. Unexpectedly, we also observed enhanced autocrine production of prostaglandin I2 (PGI2, also called prostacyclin) in Cav-1 KO EC, and this PGI2 increase appeared to stimulate cAMP/PKA pathways, contributing to the enhanced lipolysis in Cav-1 KO cells. Our results reveal an unanticipated role of Cav-1 in regulating lipolysis in non-adipose tissue, indicating that Cav-1 is required for LD metabolism in EC and that it regulates cAMP-dependent lipolysis in part via the autocrine production of PGI2. |
| Databáze: | OpenAIRE |
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