Silencing of human methionine adenosyltransferase 1A expression by methylation of the coding region.

This article was withdrawn by the authors before final publication on December 10, 2004.

S-adenosylmethionine in the chemoprevention and treatment of hepatocellular carcinoma in a rat model.

Unlabelled: Hepatocellular carcinoma (HCC) remains a common cancer worldwide that lacks effective chemoprevention or treatment. Chronic liver disease often leads to impaired hepatic S-adenosylmethionine (SAMe) biosynthesis, and mice with SAMe deficiency develop HCC spontaneously. SAMe is antiapoptotic in normal hepatocytes but proapoptotic in cancerous hepatocytes.

Inhibition of human betaine-homocysteine methyltransferase expression by S-adenosylmethionine and methylthioadenosine.

BHMT (betaine-homocysteine methyltransferase) remethylates homocysteine to form methionine. SAM (S-adenosylmethionine) inhibits BHMT activity, but whether SAM modulates BHMT gene expression is unknown. Transcriptional regulation of the human BHMT is also unknown.

Tumour necrosis factor alpha induces co-ordinated activation of rat GSH synthetic enzymes via nuclear factor kappaB and activator protein-1.

GSH synthesis occurs via two enzymatic steps catalysed by GCL [glutamate-cysteine ligase, made up of GCLC (GCL catalytic subunit), and GCLM (GCL modifier subunit)] and GSS (GSH synthetase). Co-ordinated up-regulation of GCL and GSS further enhances GSH synthetic capacity. The present study examined whether TNFalpha (tumour necrosis factor alpha) influences the expression of rat GSH synthetic enzymes.

Nrf1 and Nrf2 regulate rat glutamate-cysteine ligase catalytic subunit transcription indirectly via NF-kappaB and AP-1.

Glutamate-cysteine ligase catalytic subunit (GCLC) is regulated transcriptionally by Nrf1 and Nrf2. tert-Butylhydroquinone (TBH) induces human GCLC via Nrf2-mediated trans activation of the antioxidant-responsive element (ARE). Interestingly, TBH also induces rat GCLC, but the rat GCLC promoter lacks ARE.

WITHDRAWN: Silencing of human methionine adenosyltransferase 1A expression by methylation of the coding region.

Two genes (MAT1A and MAT2A) encode for the essential enzyme methionine adenosyltransferase (MAT). MAT1A is silenced in hepatocellular carcinoma (HCC), and absence of MAT1A leads to spontaneous development of HCC in mice. Here we investigated the role of methylation in regulating MAT1A expression.

S-adenosylmethionine and its metabolite induce apoptosis in HepG2 cells: Role of protein phosphatase 1 and Bcl-x(S).

S-adenosylmethionine (SAMe) and its metabolite 5'-methylthioadenosine (MTA) are proapoptotic in HepG2 cells. In microarray studies, we found SAMe treatment induced Bcl-x expression. Bcl-x is alternatively spliced to produce two distinct mRNAs and proteins, Bcl-x(L) and Bcl-x(S).

Induction of human methionine adenosyltransferase 2A expression by tumor necrosis factor alpha. Role of NF-kappa B and AP-1.

Two genes (MAT1A and MAT2A) encode for methionine adenosyltransferase (MAT), an essential cellular enzyme responsible for S-adenosylmethionine biosynthesis. MAT1A is expressed mostly in the liver, whereas MAT2A is widely distributed. We showed a switch from MAT1A to MAT2A expression in human hepatocellular carcinoma (HCC), which facilitates cancer cell growth.

Role of AP-1 in the coordinate induction of rat glutamate-cysteine ligase and glutathione synthetase by tert-butylhydroquinone.

GSH synthesis occurs via two enzymatic steps catalyzed by glutamate-cysteine ligase (GCL, made up of two subunits) and GSH synthetase (GS). Recently, we described coordinate induction of GCL subunits and GS. To study GS transcriptional regulation, we have cloned and characterized a 2.