Development of new drug for intractable hyperlipidemia and its clinical application

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We found apolipoprotein B-100 (apo B) secretion is regulated in response to the change of intracellular cholesteryl ester contents by adding low density lipoprotein (LDL). LDL caused a significant dose-dependent increase in apo B secretion, because of preventing the degradation of apo-B protein itself. Immediately after apo B protein is translated from mRNA of apo B,microsomal triglyceride transfer protein (MTP) makes assembly with apo B protein. As a result, VLDL particles are formed. Therefore MTP plays an important role for regulating VLDL production and secretion. To investigate this regulation, we first cloned full length of cDNA for MTP,succeeded to transfect MTP cDNA to CHO cells and detected MTP protein. We are now doing following experiments.1) To establish MTP overexpression system in rabbit hepatocytes.2) To establish transgenic mouse which over express MTP cDNA using transferin promoter.3) To analyze proteins which could regulate post-translational modification of apo-B protein, suchi as MTP,HDP-70 and unknown protein.