title: The disturbance of hippocampal CaMKII/PKA/PKC phosphorylation in early experimental diabetes mellitus.
abstract: BACKGROUND
  Defining the impact of diabetes and related risk factors on brain cognitive function is critically important for patients with diabetes.
  
  
  OBJECTIVE
  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.
authors.affiliation: Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, Zhejiang University, Hangzhou, China.
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: Liao
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Xiang
authors.forename: Ji-Yun
authors.initials: JY
authors.lastname: Huang
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Tao
authors.forename: Yun
authors.initials: Y
authors.lastname: Tian
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Ye
authors.forename: Gen-Sheng
authors.initials: GS
authors.lastname: Zhang
authors.forename: Ying-Mei
authors.initials: YM
authors.lastname: Lu
authors.forename: Muhammad M
authors.initials: MM
authors.lastname: Ahmed
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Liu
authors.forename: Kohji
authors.initials: K
authors.lastname: Fukunaga
authors.forename: Feng
authors.initials: F
authors.lastname: Han
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D054645:Protein Phosphatase 1 / Q000032:analysis; D054648:Protein Phosphatase 2 / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D013311:Streptozocin; D016704:Synapsins / Q000378:metabolism
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; D018091:Receptors, AMPA; D013311:Streptozocin; D016704:Synapsins