SR-BI, CD36, and caveolin-1 contribute positively to cholesterol efflux in hepatic cells.
In non-hepatic cells, scavenger receptor class B type I (SR-BI), cluster of differentiation 36 (CD36), and caveolin-1 were described as mediators of cholesterol efflux, the first step of reverse cholesterol transport (RCT). Stable transformants of HepG2 cells overexpressing SR-BI, CD36, or caveolin-1 were generated, as well as cells overexpressing both caveolin-1 and SR-BI or caveolin-1 and CD36 in order to address the effect of caveolin-1 on both receptor activities. These cells were analyzed for their ability to efflux cholesterol to HDL(3). Our results show that overexpressing SR-BI, CD36, or caveolin-1 increases cholesterol efflux by 106, 92, and 48%, respectively. Moreover, the dual overexpressions of caveolin-1 and SR-BI or caveolin-1 and CD36 lead to a more prominent increase in cholesterol efflux. Studies were also conducted with primary cultures of SR-BI knockout (KO), CD36 KO, and SR-BI/CD36 double-KO (dKO) mice. SR-BI KO and SR-BI/CD36 dKO hepatic cells show 41 and 56% less cholesterol efflux, respectively, than normal hepatic cells. No significant difference was observed between the efflux of normal and CD36 KO cells. The difference between the role of human and murine CD36 correlated with the absence of CD36 dimers in mouse caveolae/rafts. Overall, our results show that SR-BI is clearly involved in cholesterol efflux in mouse and human hepatic cells, while CD36 plays a significant role in human cells.
Truong
To Quyen
TQ
Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Québec, Canada.
Aubin
Dominique
D
Falstrault
Louise
L
Brodeur
Mathieu R
MR
Brissette
Louise
L
D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D005260:Female; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism*
D018955:CD36 Antigens; D051242:Caveolin 1; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D002784:Cholesterol