Functional analysis of human ABC transporters involved in HDL generation.

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Cholesterol is an essential component for our body as a constituent of plasma membrane and precursor of steroid hormones. Since the excess cholesterol is harmful to cells, cholesterol homeostasis in peripheral tissues are tightly regulated. In this research, we purified human ABCG1 and ABCG4, and analyzed its substrate specificity by measuring ATPase activity.Purified ABCG1 showed the ATPase activity that comparable to those of active transporters. The ATPase activity of ABCG1, reconstituted in phosphatidylserine liposome, was stimulated by cholesterol and choline phospholipids (especially sphingomyelin). The ATPase activity of ABCG4 was stimulated in cholesterol containing liposomes. Unlike ABCG1, choline phospholipids showed no effects on the ATPase activity. Our results suggest that ABCG1 and ABCG4 are active lipid transporters and ABCG1 recognizes cholesterol and sphingomyelin as transport substrates, while ABCG4 is a cholesterol specific transporter.