Inhibition of thymidylate synthase and thymidine kinase by okadaic acid in regenerating rat liver after partial hepatectomy.
The effects of okadaic acid, a potent and specific inhibitor of protein phosphatases 1 and 2A, on liver regeneration after partial (70%) hepatectomy were investigated. The injection of okadaic acid (25 micrograms/kg body weight) inhibited the increases in the activities of thymidylate synthase and thymidine kinase in regenerating rat liver at 24 hr after partial hepatectomy, with a concomitant reduction in DNA content. Northern blot analysis showed that the suppression of thymidylate synthase and thymidine kinase activities was caused by comparable decreases in their mRNA levels. The protein levels of thymidylate synthase and thymidine kinase were confirmed by immunoblotting assay to be proportional to the activity and mRNA levels. These findings suggest that okadaic acid-sensitive protein phosphatases are involved in transcriptional control of the dTMP-synthesizing enzymes during liver regeneration.
Tsukamoto
I
I
Department of Food Science and Nutrition, Nara Women's University, Japan.
Yoshida
Y
Y
Kitamura
Y
Y
Nomura
S
S
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006498:Hepatectomy; D008099:Liver / Q000187:drug effects*; D008297:Male; D019319:Okadaic Acid; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000187:drug effects; D013937:Thymidine Kinase / Q000187:drug effects*; D013940:Thymidylate Synthase / Q000187:drug effects*
D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D019319:Okadaic Acid; D013940:Thymidylate Synthase; D013937:Thymidine Kinase