Habermann E, Weller U, Hudel M
Rudolf-Buchheim-Institut für Pharmakologie, Justus-Liebig-Universität Giessen, Federal Republic of Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1991 Mar;343(3):323-9. doi: 10.1007/BF00251134.
Single-chain toxin was investigated in vitro and in vivo for limited proteolysis into the fully active two-chain toxin. Plasmin from serum, elastase and gelatinase from leucocytes, as well as clostripain from C. histolyticum cleaved single-chain toxin and increased by that way its ability to inhibit [3H]noradrenaline release in vitro. Cultured mouse brain generated fragments from 125I-single-chain toxin which were cell-associated. Some of them comigrated in electrophoresis with light and heavy chain after mercaptolysis. When injected i.v. into rats, 125I-single-chain-toxin disappeared from the blood with a half-life of about 11 h without signs of nicking. However, after its injection into the triceps surae muscle both single- and two-chain toxin were found in the ipsilateral ventral horn of the spinal cord. Thus single-chain toxin is subjected to limited proteolysis by enzymes involved in tissue damage, by cultured brain tissue, and during or after its retrograde axonal transport to the spinal cord. Limited proteolysis is necessary for the release of the light chain known to mediate the action of toxin on several systems.
对单链毒素进行了体外和体内研究，以探究其有限蛋白水解为完全活性的双链毒素的情况。血清中的纤溶酶、白细胞中的弹性蛋白酶和明胶酶，以及溶组织梭菌的梭菌蛋白酶均可切割单链毒素，从而增强其体外抑制[3H]去甲肾上腺素释放的能力。培养的小鼠脑可从125I-单链毒素产生与细胞相关的片段。其中一些片段在巯基裂解后在电泳中与轻链和重链共迁移。静脉注射到大鼠体内后，125I-单链毒素以约11小时的半衰期从血液中消失，且无切口迹象。然而，将其注射到腓肠肌后，在脊髓同侧腹角中发现了单链和双链毒素。因此，单链毒素在组织损伤相关酶、培养的脑组织以及逆行轴突运输至脊髓期间或之后，会受到有限的蛋白水解作用。有限的蛋白水解对于释放已知介导毒素对多个系统作用的轻链是必要的。
