The Mechanism Of Glial Cell Selective Affected In VWM

BackgroundLeukoencephalopathy with vanishing white matter (VWM, OMIM # 603896),is an autosomal recessive transmitted leukoencephalopathy. This is the first time that mutations in genes encoding subunits of a translation factor have been implicated in VWM in 2001-2002.[2] A genetic-linkage study showed that VWM is caused by mutations in the genes encoding the five subunits of eukaryotic initiation factor 2B (eIF2B). Mutations in any of the five genes encoding the subunits of eukaryotic initiation factor 2B (eIF2B) can cause VWM.eIF2B exists in all eukaryotic cells, but only cerebral white matter is damaged.eIF2B plays a crucial role in protein synthesis at initiation step in all cell. The important role of eIF2B through eIF2 to achieve. The function of eIF2B was mainly adjusted by eIF2a phosphorylation and eIF2B-e phosphorylation. Because the levels of eIF2 are often higher than the levels of eIF2B, even small changes in the level of phosphorylation of eIF2 can impair the activity of eIF2B. So lead to the protein synthesis is decline.The eIF2B complex consists of five subunits (α-ε), and identify multiple phosphorylation sites in the largest, catalytic, subunit (ε) of mammalian eIF2B. There has some phosphorylation sites and control its activity by phosphorylation. Although in severe VWM variants multiple organs can be affected,the fact that the cerebral white matter is predominantly affected in VWM is still unexplained. Whether glial cell may have some control mechanism of eIF2B different from other tissues to lead to affectivity, this is a main problem to discuss of this research. Objective(1) The basis eIF2α/eIF2B-e ratio of glial cell may be significantly higher than in other organizations such as cortex,hear,liver,kidney and skeletal.(2) Under basal conditions phospho-eIF2a(ser51) level of glial cells may be higher than other organizations.(3) Under basal conditions phosphor-eIF2B-e (ser535) level of glial cells may be higher than other organizations.MethodsDissected the tissues of striatum,cortex,heart,live,kidney and skeletal from wistar rats of 12 days old(Roughly equivalent to the human infant and early childhood) then extracted total protein from different tissues. of The level of proteins was determined by Western blot to analyze the basis eIF2α/eIF2B-e ratio in Cerebral white matter and other tissues. And the level of proteins was determined by Western blot to analyze the basis eIF2a Ser51(P)/eIF2a ratio in Cerebral white matter and other tissues. Last the level of proteins was determined by Western blot to analyze the basis eIF2Be Ser535(P)/eIF2Be ratio in Cerebral white matter and other tissues.ResultsWhen total neuronal protein was examined, the basis eIF2a/eIF2B-e of cerebral white matter (glial cell) has a slightly increasing trend compared with that of cortex, heart, liver, kidney and skeletal muscle. May be due to the number of test cases is too small, thus did not show statistically significant. The result was that phosphorylated eIF2a/eIF2a of Cerebral white matter (glial cell) is significantly higher than phosphorylated eIF2a/eIF2a of hear,liver,kidney and skeletal in rats. But cerebral white matter has not significantly difference compared with cortex. The phosphorylated eIF2B-e/eIF2B-e of cerebral white matter (glial cell) is significantly higher than phosphorylated eIF2B-e/eIF2B-e of heart,liver,kidney and skeletal in rats. But cerebral white matter has not significantly difference compared with cortex.ConclusionCerebral white matter has different levels of eIF2B regulation in comparison with other important organs and tissues. It can provide very important clues to the susceptibility of glial cells.And provides the experimental foundation for looking for more specific therapeutic targets and new therapeutic strategies.