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The Disturbance of Hippocampal C a MKII / PKA / PKC Phosphorylation in Early Experimental Diabetes Mellitus

机译:早期实验性糖尿病大鼠海马C a MKII / PKA / PKC磷酸化紊乱。

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Summary Background Defining the impact of diabetes and related risk factors on brain cognitive function is critically important for patients with diabetes. Aims To investigate the alterations in hippocampal serine/threonine kinases signaling in the early phase of type 1 and type 2 diabetic rats. Methods Early experimental diabetes mellitus was induced in rats with streptozotocin or streptozotocin/high fat. Changes in the phosphorylation of proteins were determined by immunoblotting and immunohistochemistry. Results Our data showed a pronounced decrease in the phosphorylation of Ca2+/calmodulin‐dependent protein kinase II (Ca MKII ) in the hippocampi of both type 1 and type 2 diabetic rats compared with age‐matched control rats. Unexpectedly, we found a significant increase in the phosphorylation of synapsin I ( S er 603) and G lu R 1 ( S er 831) in the same experiment. In addition, aberrant changes in hippocampal protein kinase C ( PKC ) and protein kinase A ( PKA ) signaling in type 1 and type 2 diabetic rats were also found. Moreover, PP 1α and PP 2 A protein levels were decreased in the hippocampus of type 1 diabetic rats, but significantly up‐regulated in type 2 diabetic rats. Conclusions The disturbance of Ca MKII / PKA / PKC phosphorylation in the hippocampus is an early change that may be associated with the development and progression of diabetes‐related cognitive dysfunction.
机译:发明背景定义糖尿病和相关危险因素对脑认知功能的影响对糖尿病患者至关重要。目的探讨1型和2型糖尿病大鼠早期海马丝氨酸/苏氨酸激酶信号转导的变化。方法用链脲佐菌素或链脲佐菌素/高脂大鼠诱导早期实验性糖尿病。通过免疫印迹和免疫组织化学确定蛋白质磷酸化的变化。结果我们的数据显示,与年龄匹配的对照大鼠相比,1型和2型糖尿病大鼠海马中Ca2 + /钙调蛋白依赖性蛋白激酶II(Ca MKII)的磷酸化明显降低。出乎意料的是,我们在同一实验中发现突触素I(S er 603)和Glu R 1(S 831)的磷酸化显着增加。另外,还发现1型和2型糖尿病大鼠海马蛋白激酶C(PKC)和蛋白激酶A(PKA)信号转导异常。此外,在1型糖尿病大鼠的海马中PP1α和PP 2 A蛋白水平降低,但在2型糖尿病大鼠中海马PP1α和PP 2 A蛋白水平显着上调。结论海马Ca MKII / PKA / PKC磷酸化紊乱是一种早期变化,可能与糖尿病相关的认知功能障碍的发生和发展有关。

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