title: Limited proteolysis of single-chain tetanus toxin by tissue enzymes, in cultured brain tissue and during retrograde axonal to the spinal cord.
abstract: 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.
authors.affiliation: Rudolf-Buchheim-Institut für Pharmakologie, Justus-Liebig-Universität Giessen, Federal Republic of Germany.
authors.forename: E
authors.initials: E
authors.lastname: Habermann
authors.forename: U
authors.initials: U
authors.lastname: Weller
authors.forename: M
authors.initials: M
authors.lastname: Hudel
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D001921:Brain / Q000201:enzymology*; D002478:Cells, Cultured; D010450:Endopeptidases / Q000378:metabolism; D007457:Iodine Radioisotopes; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000201:enzymology*; D013744:Tetanus Toxin / Q000378:metabolism*
chemical_list: D007457:Iodine Radioisotopes; D013744:Tetanus Toxin; D010450:Endopeptidases