The xenobiotic methionine sulfoximine modulates carbohydrate anabolism and related genes expression in rodent brain.

Methionine sulfoximine is a xenobiotic amino acid derived from methionine. One of its major properties is to display a glycogenic activity in the brain. After studying this property, we investigate here a possible action of this xenobiotic on the expression of genes related to carbohydrate anabolism in the brain. Glycogen was studied by the means of electron microscopy. Astrocytes were cultured and the influence of methionine sulfoximine on carbohydrate anabolism in these cells was investigated. In vivo, methionine sulfoximine induced a large increase in glycogen accumulation. It also enhanced the glycogen accumulation in cultured astrocytes principally, when the medium was enriched in glucose. The gluconeogenic enzyme fructose-1,6-bisphosphatase may account for glycogen accumulation. Plasmids were built using antisens cDNA to permanently block the expression of fructose-1,6-bisphosphatase. An eukaryotic vector was used and the expression of fructose-1,6-bisphosphatase gene was under the control of the promoter of the glial fibrillary acidic protein. In this case, the glycogen content in cultured astrocytes largely decreased. This work shows that methionine sulfoximine enhances energy carbohydrate synthesis in the brain. Since this xenobiotic also enhances the expression of some genes related to one of the key step of glucose synthesis, it is possible that genes may be one target of methionine sulfoximine. Next investigations will study the actual effect of methionine sulfoximine in the cells.