| Co-Investigator(Kenkyū-buntansha) |
TSUJITA Maki Nagoya City University Medical School, Research Associate, 医学部, 助手 (10253262)
DOHMAE Sumiko (ABE Sumiko) Nagoya City University Medical School, Assistant Professor, 医学部, 講師 (70227700)
ITO Jinichi Nagoya City University Medical School, Associate Professor, 医学部, 助教授 (60167260)
AOTSUKA Tomoshi Grelan Pharmaceutical Co. Ltd., Manager, 化学研究グループ, 課長
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| Research Abstract |
During the current grant term, research accomplishment is summarized below for the mechanism and physiological relevance of HDL assembly by apolipoprotein-cell interaction. Inhibition of the HDL assembly reaction by an HDL-lowering drug probucol was reproduced in mice in vivo, and demonstrated the this reaction is a main source of plasma HDL (BBA 1485 : 199, 2000) and the main organ for the reaction is the liver (ATVB 21, 394, 2001). Assembly of HDL in mouse monocytic leukemia cell RAW 264 is induced by cAMP in parallel with physical binding of apolipoprotein to the cell, and with 10-tome increase of abca1 mRNA (Biochemistry 39, 11092, 2000). From the experiments with THP-1 cells and fibroblasts, it was revealed that ABCA1 is not absolute requirement for the HDL assembly, that caveolin-1 plays an important role in incorporation of cholesterol into the HDL, and that progesterone inhibits this pathway by an unknown mechanism (JLR 41, 1952, 2000 ; JBC277, 7929, 2002 ; BBA 1532, 173, 2001). Membrane raft was suggested to be a site for the HDL assembly (JLR41, 894, 2000). When ABCA1 is transfected and functionally expressed in HEK293, the protein was shown with a signal peptide cleaved and the N-terminal exposed to outside (BBRC 283, 1019, 2001). A part of the results above is summarized in a review article (BBA 1529, 231, 2000).
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