Ethanol represses thymidylate synthase and thymidine kinase at mRNA level in regenerating rat liver after partial hepatectomy

• Published in: Biochimica et biophysica acta 1997-08, Vol.1336 (2), p.180-186
• Main Authors: Yoshida, Yuki, Komatsu, Masami, Ozeki, Ayumi, Nango, Rieko, Tsukamoto, Ikuyo
• Format: Article
• Language: English
• Subjects: Animals; Aspartate Aminotransferases - blood; DNA synthesis; Enzyme Repression - drug effects; Ethanol; Ethanol - pharmacology; Hepatectomy; Liver - drug effects; Liver - enzymology; Liver Regeneration; Male; Organ Size - drug effects; Rat; Rats; Rats, Wistar; RNA, Messenger - analysis; Signal Transduction - drug effects; Thymidine kinase; Thymidine Kinase - biosynthesis; Thymidine Kinase - drug effects; Thymidylate synthase; Thymidylate Synthase - biosynthesis; Thymidylate Synthase - drug effects
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/S0304-4165(97)00025-1

The effects of ethanol on liver regeneration after partial hepatectomy were investigated. The injection of ethanol inhibited the increases in the activities of thymidylate synthase and thymidine kinase in regenerating rat liver at 24 h after partial hepatectomy in a dose-dependent manner, with a concomitant reduction in DNA content. Northern blot analysis showed that the inhibition of thymidylate synthase and thymidine kinase activities was caused by comparable decreases in their mRNA levels. The immunoblotting assay confirmed the protein levels of thymidylate synthase and thymidine kinase as proportional to the activity and mRNA levels. These findings suggest that ethanol inhibits DNA synthesis by the repression of mRNA levels of dTMP-synthesizing enzymes during liver regeneration.