Aoki Y, Tanigawa K, Itoh H
J Toxicol Sci. 1986 Aug;11(3):145-54. doi: 10.2131/jts.11.145.
Cholestatic liver injury was experimentally induced in rats by administration of alpha-naphthylisothiocyanate (ANIT) and the peak activity of mitochondrial L-aspartate: 2-oxoglutarate aminotransferase (m-GOT) released in the serum was found to precede the peak of total GOT activity. To investigate the permeability of the mitochondrial inner membrane to m-GOT, liver mitochondria obtained from rats given ANIT were fractionated into two subfractions: one containing the matrix and the inner and outer membranes, and the other containing the intermembrane space, and the m-GOT in these fractions was determined. As a result, 12 hours after ANIT administration, the relative activity of GOT in the subfraction containing the matrix and the membranes was significantly lower than the control value. In the same period, the ratio of GOT activity to the activity of glutamate dehydrogenase, which is a marker enzyme for the matrix, and the ratio of GOT activity to the activity of cytochrome c oxidase, which is a marker enzyme for the inner membrane, were both decreased by half. In contrast, the relative GOT activity for the subfraction containing the intermembrane space was significantly increased 12 hours after administration. Also, the ratio of GOT activity to the activity of adenylate kinase, a marker enzyme for the intermembrane space, was doubled. These results suggest that m-GOT, which is originally located in the mitochondrial matrix, transmigrated to the intermembrane space via the inner membrane under the effect of ANIT administration.
通过给予大鼠α-萘异硫氰酸酯（ANIT）在实验中诱导胆汁淤积性肝损伤，发现血清中释放的线粒体L-天冬氨酸：2-氧代戊二酸氨基转移酶（m-GOT）的峰值活性先于总GOT活性的峰值。为了研究线粒体内膜对m-GOT的通透性，将给予ANIT的大鼠肝脏线粒体分离为两个亚组分：一个包含基质以及内膜和外膜，另一个包含膜间隙，并测定这些组分中的m-GOT。结果，给予ANIT后12小时，包含基质和膜的亚组分中GOT的相对活性显著低于对照值。在同一时期，GOT活性与作为基质标记酶的谷氨酸脱氢酶活性的比值以及GOT活性与作为内膜标记酶的细胞色素c氧化酶活性的比值均降低了一半。相反，给予后12小时，包含膜间隙的亚组分的相对GOT活性显著增加。此外，GOT活性与作为膜间隙标记酶的腺苷酸激酶活性的比值增加了一倍。这些结果表明，原本位于线粒体基质中的m-GOT在给予ANIT的作用下通过内膜迁移到膜间隙。
