Changes in the expression of methionine adenosyltransferase genes and S-adenosylmethionine homeostasis during hepatic stellate cell activation.

Unlabelled: Hepatic stellate cell (HSC) activation is an essential event during liver fibrogenesis. Methionine adenosyltransferase (MAT) catalyzes biosynthesis of S-adenosylmethionine (SAMe), the principle methyl donor. SAMe metabolism generates two methylation inhibitors, methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH).

Mechanisms of protection by the betaine-homocysteine methyltransferase/betaine system in HepG2 cells and primary mouse hepatocytes.

Unlabelled: Betaine-homocysteine methyltransferase (BHMT) regulates homocysteine levels in the liver. We previously reported that the alteration of BHMT is associated with alcoholic liver steatosis and injury. In this study, we tested whether BHMT protects hepatocytes from homocysteine-induced injury and lipid accumulation.

Role of methionine adenosyltransferase 2A and S-adenosylmethionine in mitogen-induced growth of human colon cancer cells.

Background & Aims: Two genes (MAT1A and MAT2A) encode for methionine adenosyltransferase, an essential enzyme responsible for S-adenosylmethionine (SAMe) biosynthesis. MAT1A is expressed in liver, whereas MAT2A is widely distributed. In liver, increased MAT2A expression is associated with growth, while SAMe inhibits MAT2A expression and growth.

Increased susceptibility of glutathione peroxidase-1 transgenic mice to kainic acid-related seizure activity and hippocampal neuronal cell death.

Glutathione peroxidase (GSHPx) has been demonstrated in several in vivo studies to reduce both the risk and severity of oxidatively-induced tissue damage. The seizure-inducing neurotoxin kainic acid (KA) has been suggested to elicit its toxic effects in part via generation of oxidative stress. In this study, we report that expression of elevated levels of murine GSHPx-1 in transgenic mice surprisingly results in increased rather than decreased KA susceptibility including increased seizure activity and neuronal hippocampal damage.

In vitro hepatotoxicity of the cyanobacterial alkaloid cylindrospermopsin and related synthetic analogues.

Cylindrospermopsin (CY), a sulfate ester of a tricyclic guanidine substituted with a hydroxymethyluracil, is a cyanobacterial toxin of increasing environmental import as it frequently occurs in drinking water reservoirs. As a toxin, CY mainly targets the liver but also involves other organs. In hepatocytes CY inhibits the synthesis of protein and of glutathione, leading to cell death.