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HDL-apoAI and its isoproteins kinetics in rabbits and gene expressin of apoAI.

HDL-apoAI 及其同种蛋白在兔体内的动力学及 apoAI 基因表达。

基本信息

批准号：
02671114
负责人：
SAKU Keijiro
金额：
$ 1.02万
依托单位：
Fukuoka Univesity School of Medicine, 2nd Department of Internal Medicine.
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02671114/
关键词：
high density lipoprotein apolipoprotein AI turnover study mRNA rabbit

项目摘要

The metabolic turnover of HDL-apolipoproteins has been studied in human, and such studies have led to a better understanding of the mechanism of low and high plasma HDL levels. We attempted here to determine the kinetic parameters (turnover) of HDL apo AI in V, WHHL rabbits, normal Japanese white (control) rabbits, with or without cholesterol, probucol feeding. ^<125>I-labeled HDL was injected intravenously and blood samples were taken periodically for 6 days. Kinetic parameters were calculated from the apo AI specific radioactivity decay curves. We found that 1) the deficiency of plasma HDL-apo AI in the WHHL rabbits resulted from an increase in FCR and a decrease in apo AI synthesis, 2) apo AI FCR of the rabbits fed cholesterol was significantly increased but there were no change in synthetic rate, and 3) the decreased HDL or apo AI seen with probucol was apparently the result of an increase in FCR and a decrease in synthesis of HDL-apo AI, compared to findings in normal chow fed rab … More bits. A decreased synthesis of apo AI remained evident even 1 month after discontinuing probucol. The action of probucol on the intracellular synthetic process of apo AI was revealed by the reduced synthesis of proapo AI.Total RNA was isolated from rabbit intestine under various conditions as stated above, ^<32>P-labeled human apo AI cDNA probe was hybridized to RNA and specific hybridization was visualized by autoradiography. Compared to findings in normal rabbits, the WHHL had 2-3 fold lower levels of intestinal apo AI mRNA, but probucol treated rabbits showed no changes in mRNA level of apo AI. Probucol may affect the extracellular, post-translational process of apo AI, thus decreasing the levels of apo AI.In vivo conversion of recombinant human proapoplipoprotein AI (rh-Met-proapo AI) from E. coli to apolipoprotein (apo) AI was also investigated in rabbits in vivo. It was found that the radioactivity of rh-Met-proapo AI migrated to more acidic isoproteins, the conversion was complete within 24 hours. Thus, 1) the proteolytic cleavage of proapo AI is an extracellular event, 2) the converting enzyme from rabbits is functional for human proapo AI processing, and 3) the injection of rh-Met-proapo AI into rabbits facilitates understanding of the early events of HDL biogenesis in rabbits. Less

HDL-载脂蛋白的代谢周转已在人体中进行了研究，这些研究已导致更好地理解低和高血浆HDL水平的机制。我们试图在此测定V、WHHL兔、正常日本白色（对照）兔（有或无胆固醇、普罗布考喂养）HDL载脂蛋白AI的动力学参数（周转）。静脉<125>注射13 I标记的HDL，并定期采集血液样品，持续6天。根据载脂蛋白AI比放射性衰变曲线计算动力学参数。结果表明：（1）WHHL兔血浆HDL-apo AI的缺乏是由于FCR增加和apo AI合成减少所致;（2）高脂饲料兔的apo AI FCR显著增加，但合成率无明显变化;（3）普罗布考引起的HDL或apo AI降低，显然是FCR增加和HDL-apo AI合成减少所致。与正常饲料喂养的rab中的发现相比， ...更多信息比特.即使停用普罗布考1个月后，载脂蛋白AI的合成仍明显减少。在上述各种条件下，从兔小肠中提取总RNA，用~（13）<32>P标记人apo AI cDNA探针与RNA杂交，放射自显影显示特异性杂交。与正常兔相比，WHHL组小肠apo AI mRNA水平降低2-3倍，而普罗布考组无明显变化。普罗布考可能影响apo AI的胞外翻译后过程，从而降低apo AI的水平。在家兔体内研究了大肠杆菌对载脂蛋白AI的影响。发现rh-Met-proapo AI的放射性迁移到酸性更强的同种蛋白，在24小时内完全转化。因此，1）proapo AI的蛋白水解裂解是一种细胞外事件，2）来自兔的转化酶对人proapo AI加工具有功能，3）将rh-Met-proapo AI注射到兔中有助于了解兔中HDL生物合成的早期事件。少