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Interactions of hepatotoxic agents with proteins and subcellular structures
Authors:H. Faulstich
Affiliation:Max-Planck-Institute for Medical Research, Dept. of Natural Products Chemistry, Jahnstr. 29, 6900 Heidelberg, F.R.G.
Abstract:Two proteins with high affinity for amatoxins have been characterized in calf thymus nucleic, the RNA-polymerase II (or B) and a 100 K protein of unknown function. Most of the toxic effects of amatoxins are based on the inhibited synthesis of mRNA. The 100 K protein may be involved in functions of cytokinesis as suggested by experiments with PtK1 cells and a fluorescent labelled amatoxin. The molecular toxicity of phallotoxins can be understood in terms of their affinity for actin. By interaction with rabbit muscle actin the concentration of action monomers is decreased. In hepatocytes, the phallotoxins change the structure of the microfilamentous web.
Keywords:TAC  thioacetamide  AT  3-amino-1,2,4-triazole  MET  metyrapone  SKF 525 A  2-diethylaminoethyl 2,2-diphenylvalerate hydrochloride  Lilly 18947  2,4 dichloro-6-phenoxyethyl diethylamine hydrochloride  Sch 5705  ethyl 2-diethylaminoethyl-2-phenyl-2-ethylmalonate hydrobromide  Sch 5712  ethyl-2- diethylaminoethyl-2-ethyl-buthylmalonate hydrobromide  MMI  1-methyl-2-mercaptoimidazole  TMA  trimethylamine hydrochloride  IM  imipramine  DPH  diphenhydramine hydrochloride  NIC  nicotinamide  CFT 1201  2-diethylaminoethyl-2-phenyl-2(2-propene)- 4-penten-1-oate hydrochloride  AP  aminopyrine  DDTC  diethyldithiocarbamic acid sodium salt  TU  thiourea  DS  tetraethyl thiuramdisulfide (disulfiram)  CYST  cystamine dihydrochloride  PB  sodium phenobarbital  ICD  plasma isocitric acid dehydrogenase
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