The xenobiotic methionine sulfoximine modulates carbohydrate anabolism andrelated 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 brai n. After studying this property, we investigate here a possible action of t his xenobiotic on the expression of genes related to carbohydrate anabolism in the brain. Glycogen was studied by the means of electron microscopy. As trocytes were cultured and the influence of methionine sulfoximine on carbo hydrate anabolism in these cells was investigated. In vivo, methionine sulf oximine induced a large increase in glycogen accumulation. It also enhanced the glycogen accumulation in cultured astrocytes principally, when the med ium was enriched in glucose. The gluconeogenic enzyme fructose-1,6-bisphosp hatase may account for glycogen accumulation. Plasmids were built using ant isens cDNA to permanently block the expression of fructose-1,6-bisphosphata se. An eukaryotic vector was used and the expression of fructose-1,6-bispho sphatase 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 ene rgy carbohydrate synthesis in the brain. Since this xenobiotic also enhance s the expression of some genes related to one of the key step of glucose sy nthesis, it is possible that genes may be one target of methionine sulfoxim ine. Next investigations will study the actual effect of methionine sulfoxi mine in the cells. (C) 2000 Elsevier Science Ireland Ltd. All rights reserv ed.