| Abstract
| - Caveolae are 50−100 nm plasma membrane invaginations, which function in cell signalingand transcytosis, as well as in regulating cellular cholesterol homeostasis. These subcompartments of theplasma membrane are characterized by the presence of caveolin proteins. Recent studies have indicatedthat caveolae may be involved in the regulation of cellular cholesterol efflux to HDL, as well as selectiveuptake mediated by SR-BI. In the present study, we have determined the effect of caveolin-1 overexpressionin mouse liver on plasma lipoprotein metabolism. We evaluated this effect using an adenovirus-mediatedgene delivery system. C57BL/6J mice were injected with adenoviruses encoding either caveolin-1 (Adcav-1) or green fluorescent protein (AdGFP) together with a transactivator adenovirus (AdtTA). We foundthat, after adenovirus injection, caveolin-1 was overexpressed in hepatocytes. Moreover, the recombinantprotein was localized to the plasma membrane. We also found that caveolin-1 overexpression induced amarked change in the lipoprotein profile of injected animals. In caveolin-1 overexpressing animals, plasmaHDL−cholesterol levels were found to be ∼2-fold elevated, as compared with control animals. To determinethe effect of caveolin-1 on SR-BI-mediated selective uptake, we infected murine hepatocytes in culturewith an adenoviral vector carrying the caveolin-1 cDNA or GFP as a control protein. We show that, inprimary cultures of hepatocytes, caveolin-1 inhibits DiI−HDL uptake mediated by SR-BI. This resultwould mechanistically explain the increased plasma HDL−cholesterol levels we observed in caveolin-1adenovirus-injected animals. In addition, caveolin-1 expression increased the secretion of apolipoproteinA-I in cultured hepatocytes and increased apolipoprotein A-I plasma levels in mice. Our study thereforedemonstrates an important role for caveolin-1 in regulating HDL metabolism.
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