Multiple sites of control of glutathione S-transferase P1-1 in rat liver.
Glutathione transferase P1-1, normally very low in adult rat liver, is induced by a single intravenous dose of lead nitrate. In this transient induction, there are at least three sites of regulation or control. These are transcription, post-transcription, and post-translation. The increase in transcription is evident both by nuclear run-off analysis and by measurement of mRNA levels. The other two sites of control were seen in actinomycin D-treated animals in which RNA synthesis was inhibited by over 80%. Treatment with actinomycin D increases the stability of the mRNA and also somehow inhibits the conversion of a glutathione transferase protein to an enzymatically active form. These three sites offer possibilities for the study of mechanisms of control for this interesting enzyme that may play a role in chemical carcinogenesis and in drug resistance.
Koo
P
P
Department of Pathology, University of Toronto, Ontario, Canada.
Nagai
M K
MK
Farber
E
E
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005982:Glutathione Transferase / Q000096:biosynthesis*; D007527:Isoenzymes / Q000096:biosynthesis*; D007700:Kinetics; D007854:Lead / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009566:Nitrates / Q000494:pharmacology*; D009963:Orotic Acid / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
D007527:Isoenzymes; D009566:Nitrates; D012333:RNA, Messenger; D003609:Dactinomycin; D007854:Lead; D009963:Orotic Acid; C017461:lead nitrate; D005982:Glutathione Transferase