Ischemia and status epilepitcus result in enhanced phosphorylation of calcium and calmodulin-stimulated protein kinase II on threonine 253.

Abstract

Ca2+-stimulated protein kinase II (CaMKII) is critically involved in the regulation of synaptic function and is implicated in the neuropathology associated with ischemia and status epilepticus (SE). The activity and localization of CaMKII is regulated by multi-site phosphorylation. In the present study we investigated the effects of global ischemia followed by reperfusion and of SE on the phosphorylation of CaMKII on T253 in rat forebrains and compared this to the phosphorylation of T286. Both ischemia and SE resulted in marked increases in the phosphorylation of T253, and this was particularly marked in the postsynaptic density (PSD). Phosphorylation of T286 decreased rapidly towards basal levels following ischemia whereas phosphorylation of T253 remained elevated for between 1 and 6 h before decreasing to control values. Following SE, phosphorylation of T253 remained elevated for between 1 and 3 h before decreasing to control levels. In contrast, phosphorylation of T286 remained elevated for at least 24 h following the termination of SE. Total CaMKII associated with PSDs transiently increased 10 min following ischemia, but only several hours following SE. The results demonstrate that phoshorylation of CaMKII on T253 is enhanced following both ischemia/reperfusion and SE and indicate that the phosphorylation of T253 and T286 are differentially regulated.

• Authors: James W Gurd, Salma Rawof, Jeanne Zhen Huo, Crystal Dykstra, Nankie Bissoon, Lucy Teves, M Christopher Wallace, John A P Rostas
• Journal: Brain research (Brain Res) Vol. 1218 Pg. 158-65 (Jul 07 2008) ISSN: 0006-8993 [Print] Netherlands
• PMID: 18514171 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Pilocarpine
• Threonine
• Calcium-Calmodulin-Dependent Protein Kinase Type 2
• Lithium Chloride
• Calcium

Topics

• Animals
• Calcium (metabolism)
• Calcium-Calmodulin-Dependent Protein Kinase Type 2 (metabolism)
• Disease Models, Animal
• Ischemia (metabolism, pathology)
• Lithium Chloride
• Male
• Phosphorylation
• Pilocarpine
• Prosencephalon (ultrastructure)
• Rats
• Rats, Wistar
• Status Epilepticus (chemically induced, metabolism, pathology)
• Synaptosomes (metabolism)
• Threonine (metabolism)