Molecular Basis of Intracellular Cholesterol Homeostasis and Genration of HDL

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1)ABCA1 is phosphorylated by RKCa activated by diacylglycerol generated in the reactions to replenish sphingomyelin that is removed by apoA-I to generate HDL. This reaction is generally observed with helical apolipoproteins that are capable of generating HDL, as well as the model peptides mimicking amphiphilic helices of apolipoprotein. 2)Human ABCA7 that is highly homologous to ABCA1mediates generation of HDL is stabilized by apolipoproteins in a similar manner to that of ABCA1 when expressed in HEK293. 3)Release of cellular cholesterol to HDL is mediated by two distinct mechanism ; non-specific exchange and an apolipoprotein/ABCA1 mediated pathway. The latter reaction was investigated by using an anti-apoA-I monoclonal antibody that recognizes only lipid free apoA-I. This antibody inhibited the ABCA1-dependent part of the cholesterol release reaction. The ABCA1-dependent HDL abiding to cells is only its protein moiety but not the lipid part. Thus, apoA-I dissociates from HDL and interacts with the cells to generate new HDL.