These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Differential effect of thioacetamide on hepatic methionine adenosyltransferase expression in the rat.
    Author: Huang ZZ, Mato JM, Kanel G, Lu SC.
    Journal: Hepatology; 1999 May; 29(5):1471-8. PubMed ID: 10216131.
    Abstract:
    Liver-specific and non-liver-specific methionine adenosyltransferase (MAT) are products of two genes, MAT1A and MAT2A, respectively, that catalyze the formation of S-adenosylmethionine (SAM), the principal methyl donor. Mature liver expresses mainly MAT1A. We showed a switch from MAT1A to MAT2A gene expression in human liver cancer cells that may offer a growth advantage. To gain a better understanding of the chronology and significance of the change in MAT expression, we examined changes in hepatic MAT expression after acute treatment of rats with a hepatocarcinogen, thioacetamide (TAA). TAA treatment for 3 weeks did not change the MAT1A mRNA level but reduced the liver-specific MAT protein level to below 30% of control. TAA also acutely reduced the activity of liver-specific MAT when added to normal liver homogenates. In contrast, both the mRNA and protein levels of non-liver-specific MAT were induced. Because liver-specific MAT exhibits a much higher Km for methionine (mmol/L) than non-liver-specific MAT ( approximately 10 micromol/L), MAT activity was decreased at 5 mmol/L but increased at 20 micromol/L methionine concentration. The SAM level, SAM-to-S-adenosylhomocysteine (SAH) ratio, and DNA methylation all fell during treatment. In summary, TAA treatment induced differential changes in hepatic MAT expression. The reduction in liver-specific MAT protein level represents a novel mechanism of inactivation of liver-specific MAT. This along with induction in MAT2A contributed to a fall in the SAM-to-SAH ratio. The resulting DNA hypomethylation may be important in the process of hepatocarcinogenesis.
    [Abstract] [Full Text] [Related] [New Search]