早期实验性糖尿病中海马 CaMKII/PKA/PKC 磷酸化的紊乱。

The disturbance of hippocampal CaMKII/PKA/PKC phosphorylation in early experimental diabetes mellitus.

机构信息

Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, Zhejiang University, Hangzhou, China.

出版信息

CNS Neurosci Ther. 2013 May;19(5):329-36. doi: 10.1111/cns.12084. Epub 2013 Mar 14.

DOI:10.1111/cns.12084

PMID:23490331

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6493428/

Abstract

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 Ca(2+) /calmodulin-dependent protein kinase II (CaMKII) 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 (Ser 603) and GluR1 (Ser 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, PP1α and PP2A 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 CaMKII/PKA/PKC phosphorylation in the hippocampus is an early change that may be associated with the development and progression of diabetes-related cognitive dysfunction.

摘要

背景

明确糖尿病及相关危险因素对大脑认知功能的影响，对糖尿病患者至关重要。

目的

研究 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改变。

方法

采用链脲佐菌素或链脲佐菌素/高脂诱导大鼠早期实验性糖尿病。通过免疫印迹和免疫组化测定蛋白质磷酸化的变化。

结果

与年龄匹配的对照组大鼠相比，我们的数据显示，1 型和 2 型糖尿病大鼠海马中的钙/钙调蛋白依赖性蛋白激酶 II（CaMKII）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（Ser603）和 GluR1（Ser831）的磷酸化显著增加。此外，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）信号的异常变化。此外，1 型糖尿病大鼠海马中的蛋白磷酸酶 1α（PP1α）和蛋白磷酸酶 2A（PP2A）蛋白水平降低，但在 2 型糖尿病大鼠中显著上调。

结论

海马中 CaMKII/PKA/PKC 磷酸化的紊乱是一种早期变化，可能与糖尿病相关认知功能障碍的发生和发展有关。

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