Multiple sites of control of glutathione S-transferase P1-1 in rat liver

• Published in: The Journal of biological chemistry Vol. 269; no. 20; pp. 14601 - 14606
• Main Authors: KOO, P, NAGAI, M. K, FARBER, E
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 20.05.1994
• Subjects: Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Cell Nucleus - metabolism; Dactinomycin - pharmacology; Enzyme Induction; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Enzymologic - drug effects; Glutathione Transferase - biosynthesis; Isoenzymes - biosynthesis; Kinetics; Lead - pharmacology; Liver - drug effects; Liver - enzymology; Male; Nitrates - pharmacology; Orotic Acid - metabolism; Protein Processing, Post-Translational - drug effects; Rats; Rats, Inbred F344; RNA Processing, Post-Transcriptional - drug effects; RNA, Messenger - biosynthesis; RNA, Messenger - isolation & purification; RNA, Messenger - metabolism; Time Factors; Transcription, Genetic - drug effects; Transferases; Rat; Transcription; Enzyme; Transferases; Liver; Rodentia; Lead nitrate; Posttranscriptional modification; Posttranslational modification; Northern blotting; Vertebrata; Regulation(control); Mammalia; Glutathione transferase
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(17)36666-8

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.