PLASMA-CLEARANCE OF INTRAVENOUSLY INJECTED ASPARTATE-AMINOTRANSFERASE ISOZYMES - EVIDENCE FOR PREFERENTIAL UPTAKE BY SINUSOIDAL LIVER-CELLS
PLASMA-CLEARANCE OF INTRAVENOUSLY INJECTED ASPARTATE-AMINOTRANSFERASE ISOZYMES - EVIDENCE FOR PREFERENTIAL UPTAKE BY SINUSOIDAL LIVER-CELLS
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DOI：
10.1002/hep.1840050305
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发表时间：
1985-01-01
期刊：
影响因子：
13.5
通讯作者：
MORINO, Y
中科院分区：
文献类型：
--
作者：
KAMIMOTO, Y;HORIUCHI, S;MORINO, Y
天冬氨酸氨基转移酶（EC 2.6.1.1）的胞质（c-AAT）和线粒体（m-AAT）同工酶在包括肝胆功能障碍在内的一些疾病中出现在血清中。阐明了AAT同工酶从血液中清除的机制。从大鼠肝脏中纯化的m-AAT和c-AAT静脉注射到大鼠体内显示出双相清除曲线，总半衰期分别为42 min和4.7 h。静脉注射125 I标记的同工酶后放射性的组织分布表明，肝脏是参与这些同工酶血浆清除的主要器官。肝切除和CCl 4中毒大鼠中m-AAT的血浆清除率显著延迟支持了这一点。在离体灌流肝中，各AAT同工酶的清除速率均呈单指数过程，m-AAT的摄取速率远快于c-AAT。从静脉注射125 I标记的AAT同工酶的大鼠分离肝细胞和肝窦细胞显示，肝窦细胞负责血浆清除。体外摄取研究表明，这两种同工酶只被肝窦细胞摄取。m-AAT的摄取率显著高于c-AAT。内吞指数为16倍，c-AAT和m-AAT相比，菊粉或右旋糖酐，这是采取了液相内吞作用，表明参与吸附内吞作用的同功酶的摄取窦状细胞。
Both cytosolic (c-AAT) and mitochondrial (m-AAT) isozymes of aspartate aminotransferase (EC 2.6.1.1) appear in serum in some diseases including hepatobiliary dysfunction. Elucidation of the mechanism by which AAT isozymes are cleared from blood was made. I.v. injection into rats of m-AAT and c-AAT purified from rat liver exhibited a biphasic clearance curve with an overall half-life of 42 min and 4.7 h, respectively. The tissue distribution of the radioactivity following i.v. administration of 125I-labeled isozymes revealed that the liver is a major organ involved in plasma clearance of these isozymes. This was supported by the significant retardation in plasma clearance of m-AAT in hepatectomized as well as CCl4-intoxicated rats. The clearance rate of each AAT isozyme in an isolated perfused liver exhibited a single exponential process with the uptake rate for m-AAT being much faster than that for c-AAT. Separation of hepatocytes and sinusoidal liver cells from the rat injected i.v. with 125I-labeled AAT isozymes revealed that sinusoidal cells were responsible for the plasma clearances. In vitro uptake study showed that both isozymes were exclusively taken up by sinusoidal liver cells. The uptake rate for m-AAT was considerably greater than that for c-AAT. Endocytotic index for uptake by sinusoidal cells was 16 times with c-AAT and 34 times with m-AAT as compared with that for inulin or dextran which are taken up by fluid-phase endocytosis, suggesting involvement of adsorptive endocytosis in the uptake of the isozymes.