Phosphoinositide 3-kinase mediates protein kinase C βII mRNA destabilization in rat A10 smooth muscle cell cultures exposed to high glucose

摘要: High-glucose exposure down-regulates protein kinaseCβII posttranscriptionally in rat and human vascular smooth muscle cells contributes to increased cell proliferation. High-glucose-induced mRNA destabilization is specific for PKCβII mRNA, while PKCβI other PKC are not affected. This study focused on whether glucose metabolism was required. The effect blocked by cytochalasin B, suggesting a requirement uptake. Glucosamine did mimic the effect, indicating that via hexosamine pathway involved. hexokinase-independent since 3-O-methylglucose, dose-dependent manner, mimicked high-glucose effects. Cycloheximide block excluding dependency new synthesis. Wortmannin LY294002, phosphoinositide 3-kinase (PI3-kinase) inhibitors, effects presence of 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole. Glucose 3-O-methylglucose activated PI3-kinase, LY294002 Akt phosphorylation. In these cells, concentrations metabolically linked signaling independent regulate processing.