ABSTRACT
This study was designed to identify inducers of ATP-binding cassette transporter A1(ABCA1) and CD36 and lysosomal integral membrane protein-II analogous-1(CLA-1) and to evaluate the in vitro effect of the active compound on lipid metabolism. Among 20000 compounds screened, E23869 was found as a positive hit using cell-based high throughput screening models. The up-regulating activities of E23869 in ABCA1p-LUC and CLA-1p-LUC HepG2 cells were 196% and 198%, respectively. The EC50 values of E23869 in ABCA1p-LUC and CLA-1p-LUC HepG2 cells were 0.25 μmol·L-1 and 0.66 μmol·L-1, respectively. E23869 significantly upregulated the protein levels of ABCA1, scavenger receptor class B type I (SR-BI)/CLA-1 and ATP-binding cassette transporter G1(ABCG1) in both macrophages RAW264.7 and L02 cells by Western blotting analysis. Foam cell assay showed that E23869 inhibited lipids accumulations in macrophages RAW264.7. Cholesterol efflux assay showed that E23869 induced HDL-mediated cholesterol efflux in macrophages RAW264.7. Moreover, E23869 up-regulated ABCA1, SR-BI/CLA-1 and ABCG1 expressions through activation of PPARα and PPARγ. In addition, E23869 weakly promoted in vitro differentiation of mouse preadipocytes 3T3-L1. In conclusion, E23869 up-regulated ABCA1, SR-BI/CLA-1 and ABCG1 expressions to promote cholesterol efflux, which is a good leading compound for regulation of lipid metabolism.
ABSTRACT
Hepatitis C virus (HCV) cell entry is a multi step process mediated by various receptors. Among these receptors, the scavenger receptor class B type I (SR-BI) is the one considered to be the first to interact with HCV. SR-B I can bind to HCV envelope glycoprotein E2, in which the hyper variable region 1 (HVR1) segment locating at the N-terminus of E2 protein plays a critical role. The interaction of SR-BI with HCV can not only mediate HCV cell entry, but also attenuate neutralization activity of antibodies against E2 protein, contributing to the HCV immune evasion. Therefore, studying the mechanism of HCV/SR-B I interaction during cell entry can help to identify important targets in the initial step of viral infection, contributing to prevention and treatment of HCV infection. This paper reviews the current knowledge on the biological characteristics of SR-B I and mechanisms of HCV cell entry mediated by virus/SR-B I interaction.