Methionine Adenosyltransferase 2A Expression Research Articles

Regulation of human methionine adenosyltransferase 2A expression by NFkB and AP-1

activ W in tissues might also induce ATP-dependent iron transport. In this study, we induced HO1 in cultured cells and animal models with some HO1 induction factors, including Cobalt, phenylhydrazine, cis-platinum, LPS, FeSO4 and curcumin and monitored ATPdependent iron transport activity Afier 24hr treatment of wt mice, we observed a dramatic increase of lqO 1 protein ni cobalt and phenylhydrazine treated liver and kidney, concurrently, we also observed ditterent levels induction of ATP-dependent iron transport in fiver and kidney microsomes from Cobalt-treated (1,8 • 0,4 told and 1,5 • 0.1 fold, respectively) and pbenylhydrazine-treated (1.8 • 0 4 and 2.5 • 0 1 told, respectivelyi animals, In RAW 264,7 cells treated with FeSO4 and curcumin, we also found co-induction of both HO1 protein and ATP<tependent iron transport activity(more than 3-fold and more than 40-fold augnrentation respectively front curcuminand FeSO4-treated cells), Thus the data in cultured ceils and animal models implied that physiologically, the Fe-ATPase responds to iron. We are monitoring the level of Ferntm, an iron storage protein, etfected by HO1 induction factors to investigate ho`a, the cells regulate cellular iron for iron re-utflizatinn to reduce iron amounts within cells and thereby protecting cells under stress.

Hepatocyte growth factor induces MAT2A expression and histone acetylation in rat hepatocytes: role in liver regeneration.

SPECIFIC AIMSWe have studied the molecular mechanisms and mediators behind the induction of methionine adenosyltransferase 2 A (MAT2A) gene expression in the regenerating rat liver after partial he...

Role of promoter methylation in increased methionine adenosyltransferase 2A expression in human liver cancer.

Methionine adenosyltransferase (MAT), an essential enzyme that catalyzes the formation of S-adenosylmethionine (SAM), is encoded by two genes, MAT1A (liver-specific) and MAT2A (non-liver-specific). We showed a switch from MAT1A to MAT2A expression in human liver cancer, which facilitates cancer cell growth. The present work examined the role of methylation in MAT2A transcriptional regulation. We found that the human MAT2A promoter is hypomethylated in hepatocellular carcinoma, in which the gene is upregulated transcriptionally, but hypermethylated in normal liver, in which the gene is minimally expressed. Luciferase activities driven by in vitro methylated MAT2A promoter constructs were 75-95% lower than activities driven by unmethylated constructs. SAM treatment of Hep G2 cells reduced MAT2A endogenous expression by 75%, hypermethylated the MAT2A promoter, and reduced luciferase activities driven by MAT2A promoter constructs by 65-75% while not affecting MAT1A's promoter activity. Treatment of adult rat and human hepatocytes with trichostatin A, an inhibitor of histone deacetylase, upregulated MAT2A expression by more than fourfold. Collectively, these results suggest that MAT2A expression is regulated by promoter methylation and histone acetylation.

The role of c-Myb in the up-regulation of methionine adenosyltransferase 2A expression in activated Jurkat cells

Methionine adenosyltransferase (MAT) is a critical cellular enzyme which catalyses the formation of S-adenosylmethionine (SAM), the principal methyl donor. In mammals, two different genes, MAT1A and MAT2A, encode liver-specific and non-liver-specific MATs, respectively. SAM level increases during T-lymphocyte activation and is required for proliferation. A major mechanism for the increase in SAM level is increased MAT2A transcription. In the current work we examined the molecular mechanism of increased MAT2A expression in activated Jurkat cells. Treatment of Jurkat cells with interleukin-2 (IL-2), PMA or PMA plus phytohaemagglutinin (PHA) resulted in a 2-fold increase in MAT2A mRNA levels and a 2-fold increase in luciferase activity driven by the transfected human MAT2A promoter construct -571/+60 but not -270/+60. The region -571 to -270 of the human MAT2A contains a c-Myb consensus binding site. c-Myb is known to be induced during T-lymphocyte activation and its mRNA level was increased after treatment of Jurkat cells with IL-2, PMA or PMA plus PHA. Increased nuclear binding to the MAT2A c-Myb site was confirmed on electrophoretic mobility-shift and supershift analyses. Mutation of the MAT2A c-Myb site abolished the stimulatory effect of these agents on c-Myb nuclear binding and MAT2A promoter activities. Overexpression of c-Myb increased MAT2A promoter activity by 2-fold. Dexamethasone, a known inhibitor of lymphocyte activation, blocked the effect of these agents on MAT2A expression by preventing the increase in c-Myb expression.

The role of c-Myb in the up-regulation of methionine adenosyltransferase 2A expression in activated Jurkat cells

Methionine adenosyltransferase (MAT) is a critical cellular enzyme which catalyses the formation of S-adenosylmethionine (SAM), the principal methyl donor. In mammals, two different genes, MAT1A and MAT2A, encode liver-specific and non-liver-specific MATs, respectively. SAM level increases during T-lymphocyte activation and is required for proliferation. A major mechanism for the increase in SAM level is increased MAT2A transcription. In the current work we examined the molecular mechanism of increased MAT2A expression in activated Jurkat cells. Treatment of Jurkat cells with interleukin-2 (IL-2), PMA or PMA plus phytohaemagglutinin (PHA) resulted in a 2-fold increase in MAT2A mRNA levels and a 2-fold increase in luciferase activity driven by the transfected human MAT2A promoter construct -571/+60 but not -270/+60. The region -571 to -270 of the human MAT2A contains a c-Myb consensus binding site. c-Myb is known to be induced during T-lymphocyte activation and its mRNA level was increased after treatment of Jurkat cells with IL-2, PMA or PMA plus PHA. Increased nuclear binding to the MAT2A c-Myb site was confirmed on electrophoretic mobility-shift and supershift analyses. Mutation of the MAT2A c-Myb site abolished the stimulatory effect of these agents on c-Myb nuclear binding and MAT2A promoter activities. Overexpression of c-Myb increased MAT2A promoter activity by 2-fold. Dexamethasone, a known inhibitor of lymphocyte activation, blocked the effect of these agents on MAT2A expression by preventing the increase in c-Myb expression.