Cadmium induced redistribution of cholesterol by upregulating ABCA1 and downregulating OSBP

Abstract Human exposure to cadmium (Cd) could lead to alterations in lipid metabolism. However, the underlying mechanism is still unclear. In the present study, the data revealed that Cd exposure induced cholesterol redistribution both in vivo from mouse liver tissue into the serum, and in vitro from the HepG2 cells to the cultured medium, which were associated with modulating the expressions of cholesterol efflux proteins, including upregulating cholesterol exporter ATP-binding cassette transporter A1 (ABCA1) and downregulating oxysterol-binding protein (OSBP). Further investigation in HepG2 cells revealed that Cd upregulated ABCA1 expression with increased stability by inhibiting lysosomal pathway, and downregulated OSBP expression by increasing ubiquitination. Cd-induced cholesterol redistribution was completely inhibited by knockdown of ABCA1 expression using siRNA, and was significantly reduced by overexpression of OSBP. Taken together, these results suggested that Cd induced cholesterol redistribution by upregulating ABCA1 and downregulating OSBP.