Dissociation of effects on protein synthesis and ribosomes from membrane changes induced by carbon tetrachloride.
Pretreatment of rats with cycloheximide protects the liver against ribosome changes but not against alterations in the endoplasmic reticulum membrane induced by the administration of CCl(4), as observed both biochemically and ultrastructurally. Another inhibitor of protein synthesis, tenuazonic acid, has effects similar to cycloheximide. Neither compound has any apparent effect when given after the administration of CCl(4) at a time at which a major shift in ribosome distribution from polysomes to ribosome monomers or subunits has already occurred. Thus, it appears that the ribosomes are not susceptible to damage by CCl(4), or more probably an active metabolic derivative of CCl(4), when they are organized as polysomes but only when they are present as monomers or subunits. Also, unlike the situation with ethionine or puromycin, the damage to the protein synthetic system of the ribosomes induced in the liver by CCl(4) appears to be irreversible. In contrast to cycloheximide or tenuazonic acid, N,N'-diphenyl-p-phenylenediamine (DPPD) protects the liver against CCl(4)-induced changes in both ribosomes and endoplasmic reticulum. These observations suggest that the changes in the ribosome-protein synthetic system induced in the liver by treatment with CCl(4) are not the direct result of damage to the membranes of the endoplasmic reticulum but are either an indirect effect of such damage or are unrelated to it. These possibilities are discussed in terms of three proposed working hypotheses.
D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000473:pathology*; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D003513:Cycloheximide / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000473:pathology; D005001:Ethionine / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008660:Metabolism / Q000187:drug effects; D008854:Microscopy, Electron; D008899:Mineral Oil; D014176:Protein Biosynthesis; D011691:Puromycin / Q000494:pharmacology; D051381:Rats; D012270:Ribosomes / Q000187:drug effects*; D012965:Sodium Chloride
D012965:Sodium Chloride; D011691:Puromycin; D008899:Mineral Oil; D003513:Cycloheximide; D005001:Ethionine