Hyperglycemia reduces PP2A subunit B expression in a middle cerebral arteryocclusion animal model

[摘要] Diabetes is a metabolic disorder that worsens clinical outcome following cerebralischemia. Protein phosphatase 2A (PP2A) is a conserved, heterotrimeric, serine/threoninephosphatase with various cellular functions. PP2A subunit B is abundant in brain tissueand modulates PP2A function. The aim of this study was to investigate PP2A subunit Bprotein expression in the cerebral cortex of non-diabetic and diabetic animals with middlecerebral artery occlusion (MCAO) injury. Sprague-Dawley rats were injected withstreptozotocin (40 mg/kg, i.p.) to induce diabetic conditions. After 4 weeks ofstreptozotocin treatment, the rats underwent MCAO to induce focal cerebral ischemia. Thecerebral cortex tissue was collected 24 hr after MCAO. Body weight and blood glucose weremeasured, and Western blot analysis was performed to elucidate the expression of PP2Asubunit B. We confirmed decreased body weight and increased blood glucose in diabeticanimals. Reverse transcription-PCR and Western blot analyses showed decreased PP2A subunitB expression in the cerebral cortices of MCAO-injured animals. Moreover, diabetic animalswith MCAO showed more severe decreases in PP2A subunit B protein levels than non-diabeticanimals following MCAO. The decline of PP2A subunit B indicates degradation of neuronalfunction. These findings suggest that conspicuous decreases in PP2A subunit B mayexacerbate cerebral ischemia under diabetic conditions following MCAO.

[学科分类] 兽医学

[关键词] cerebral ischemia;diabetes;middle cerebral artery occlusion;PP2A subunit B