Sung Jin-Hee, Koh Phil-Ok
Department of Anatomy, College of Veterinary Medicine, Research Institute of Life Science, Gyeongsang National University, Jinju, South Korea.
J Vet Med Sci. 2017 Mar 28;79(3):654-660. doi: 10.1292/jvms.16-0437. Epub 2017 Feb 17.
Diabetes is a metabolic health disorder and an important risk factor for stroke. Phosphoprotein enriched in astrocytes 15 (PEA-15) is a multifunctional protein modulating cell proliferation, survival, apoptosis and glucose metabolism. This study investigated whether diabetes modulates the expression of PEA-15 and two phosphorylated forms (Ser 104 and Ser 116) in middle cerebral artery occlusion (MCAO)-induced brain injury. Male Sprague-Dawley rats were administrated with streptozotocin (40 mg/kg) and were underwent right middle cerebral artery occlusion (MCAO) 4 weeks after streptozotocin injection. Brain tissues were collected 24 hr after MCAO and stained using triphenyltetrazolium chloride. Western blot analysis was performed to elucidate the expression of PEA-15 and two phosphorylated forms (Ser 104 and Ser 116) in right cerebral cortex. Infarct volume during MCAO injury was severely increased in diabetic animals compared to non-diabetic animals. We identified the decrease in PEA-15 in animals that underwent MCAO using proteomic approach. PEA-15 expression during MCAO was strongly decreased in diabetic animals compared to non-diabetic animals. Western blots analysis confirmed that diabetes exacerbated the decrease in PEA-15 expression after MCAO. Moreover, decrease in expression of phospho-PEA-15 (Ser 104 and Ser 116) was greater in diabetic than in non-diabetic animals. These results suggested that a diabetic condition may aggravate brain damage through decreasing expression of PEA-15 and phospho-PEA-15 (Ser 104 and Ser 116) in ischemic brain injury.
糖尿病是一种代谢性健康障碍，也是中风的重要危险因素。富含星形胶质细胞的磷蛋白15（PEA-15）是一种多功能蛋白，可调节细胞增殖、存活、凋亡和葡萄糖代谢。本研究调查了糖尿病是否会调节大脑中动脉闭塞（MCAO）诱导的脑损伤中PEA-15及其两种磷酸化形式（Ser 104和Ser 116）的表达。给雄性Sprague-Dawley大鼠注射链脲佐菌素（40 mg/kg），并在注射链脲佐菌素4周后进行右侧大脑中动脉闭塞（MCAO）。在MCAO后24小时收集脑组织，并用氯化三苯基四氮唑染色。进行蛋白质印迹分析以阐明右侧大脑皮质中PEA-15及其两种磷酸化形式（Ser 104和Ser 116）的表达。与非糖尿病动物相比，糖尿病动物在MCAO损伤期间的梗死体积严重增加。我们使用蛋白质组学方法确定了接受MCAO的动物中PEA-15的减少。与非糖尿病动物相比，糖尿病动物在MCAO期间PEA-15的表达强烈降低。蛋白质印迹分析证实，糖尿病加剧了MCAO后PEA-15表达的降低。此外，糖尿病动物中磷酸化PEA-15（Ser 104和Ser 116）的表达降低比非糖尿病动物更大。这些结果表明，糖尿病状态可能通过降低缺血性脑损伤中PEA-15和磷酸化PEA-15（Ser 104和Ser 116）的表达来加重脑损伤。
