アラシキ　ノブト   ARASHIKI Nobuto   新敷　信人    所属   医学部 医学科    職種   助教
言語種別	日本語
発表タイトル	赤血球‐リポタンパク質間のコレステロール移動のメカニズム
会議名	第86回日本生化学会大会
学会区分	全国規模の学会
発表形式	ポスター掲示
講演区分	一般
発表者・共同発表者	◎新敷信人, 高桑雄一
発表年月日	2013/09/13
開催地 （都市, 国名）	横浜、日本
学会抄録	生化学 85(8),162 2013
概要	[Aim] Major pathogenesis of hereditary spherocytosis (HS) is dysfunction of membrane proteins. However, we recently found a patient who had erythrocytes showing the characteristics of HS without detectable abnormality in membrane proteins. This patient's erythrocytes showed remarkable increased density and decreased membrane cholesterol contents by half, suggesting that the transfer of cholesterol from erythrocytes toward lipoproteins is enhanced. The aim of this research is to clarify the molecular mechanism of the cholesterol transfer between erythrocytes and lipoproteins. [Method and Result] Erythrocytes and plasma were obtained from the blood drawn from healthy human volunteers after informed consent had been obtained. Low density lipoprotein (LDL) and high density lipoprotein (HDL) were separated from plasma by ultracentrifugation. To analyze the bidirectional transfer, washed erythrocytes and separated lipoproteins were labeled with 3H-cholesterol and mixed with non-labeled lipoproteins and erythrocytes, respectively, at equal masses of total cholesterol followed by incubation for up to 48 hr at 37C. Bidirectional transfer of 3H-cholesterol was stopped apparently at 50% of all 3H-cholesterol (Isotopic Equilibrium (IE)). Radioactive cholesterol ester was detected in HDL when non-labeled HDL was incubated with labeled erythrocytes. Inhibition of lecithin-cholesterol acyltransferase (LCAT) activity by neutral antibody or N-Ethylmaleimide resulted in decresed IE by half. IE was increased and decreased corresponding to increase and decrease in the mass of 3H-cholesterol in the acceptors, respectively. [Discussion] We confirmed that cholesterol was transferred bidirectionally between erythrocytes and lipoproteins. The mass of transferred cholesterol depended on the capacity of the acceptor. The mass, therfore, can be changed depending on the mass in the erythrocyte membrane and the surface of lipoproteins. In HDL, esterification of cholesterol from erythrocytes affected transfer of cholesterol from erythrocytes, indicating that its transfer mechanism can be distinct from that of LDL.