Interactions of hepatotoxic agents with proteins and subcellular structures.
Two proteins with high affinity for amatoxins have been characterized in calf thymus nuclei, 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 actin monomers is decreased. In hepatocytes, the phallotoxins change the structure of the microfilamentous web.
D000199:Actins / Q000378:metabolism; D000546:Amanitins / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D008099:Liver / Q000201:enzymology; D009183:Mycotoxins / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism*
D000199:Actins; D000546:Amanitins; D009183:Mycotoxins; D011506:Proteins; C018358:phallotoxin; C018207:amatoxin; D012319:RNA Polymerase II