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Ca2+/Calmodulin Dependent Protein Kinase II Subcellular Re-distribution and Activation of Protein Phosphatase After a Brief Pentylenetertrazol Seizure: Potential Role in Kindling

Dong, Yu
http://rave.ohiolink.edu/etdc/view?acc_num=mco1082463968

Abstract Details

2004, Doctor of Philosophy in Medical Sciences (Ph.D.), University of Toledo, Graduate School.
This study initially evaluated the alteration of CaMKII autophosphorylation and subcellular distribution in rat brain following a single, brief PTZ seizure. Total CaMKII á subunit and á-CaMKII phosphorylated at Thr286 were detected by immunoblot. A large decrease in CaMKII Thr286 phosphorylation, as well as CaMKII translocation from particulate to soluble fraction was evidenced in both cerebral cortex and hippocampus 0.5-4 h after the brief PTZ convulsion. These changes reverted to control values by 12 h. These long-lasting change in CaMKII autophosphorylation and subcellular distribution after a brief seizure suggested that CaMKII could be involved in carrying forward the signal resulting from the insult generated by brief seizure activity, at least for a few hours, as would be required for kindling to occur. Thus, PTZ kindling was performed, and changes in CaMKII were measured during and immediately after the completion of kindling. In PTZ kindled rats, convulsions produced changes in CaMKII Thr286 phosphorylation and distribution in the same direction and of similar magnitude as after the acute convulsion, but lasting for a much longer time. In fact, reduced Thr286 phosphorylation of á-CaMKII was observed up to 48 h, completely bridging the interval between PTZ injections. Similar, but intermediate changes were found in tissue from rats that were only partially kindled. These results implicate CaMKII as a molecular messenger in the acquisition of PTZ kindling. To answer the question of what mechanism maintains the prolonged reduction in CaMKII autophosphorylation, a brief PTZ-induce seizure was used to test the hypothesis of phosphatase activation. It was found that the reduced CaMKII Thr286 phosphorylation apparently resulted from enhanced phosphatase activity, especially in the particulate 144 fraction. Simultaneously, CaMKII translocated from particulate toward soluble fraction. Thus, CaMKII translocation and phosphatase activation might act synergistically in longlasting CaMKII regulation far outlasting the immediate effects of the seizure on neuronal function. It is then hypothesized that enhanced phosphatase activity might also be involved in modulating CaMKII autophosphorylation during PTZ kindling process. In addition, CaMKII translocation found during PTZ kindling might also play some significant role in the CaMKII-phosphatase interaction during PTZ kindling.
Howard Rosenberg, M.D., Ph.D. (Advisor)
148 p.
Biology, Neuroscience
phosphorylation; translocation; phosphatase; seizure; epilepsy; CaMuII

Recommended Citations

Citations

  • Dong, Y. (2004). Ca2+/Calmodulin Dependent Protein Kinase II Subcellular Re-distribution and Activation of Protein Phosphatase After a Brief Pentylenetertrazol Seizure: Potential Role in Kindling [Doctoral dissertation, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1082463968

    APA Style (7th edition)

  • Dong, Yu. Ca2+/Calmodulin Dependent Protein Kinase II Subcellular Re-distribution and Activation of Protein Phosphatase After a Brief Pentylenetertrazol Seizure: Potential Role in Kindling. 2004. University of Toledo, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1082463968.

    MLA Style (8th edition)

  • Dong, Yu. "Ca2+/Calmodulin Dependent Protein Kinase II Subcellular Re-distribution and Activation of Protein Phosphatase After a Brief Pentylenetertrazol Seizure: Potential Role in Kindling." Doctoral dissertation, University of Toledo, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=mco1082463968

    Chicago Manual of Style (17th edition)

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© 2003, all rights reserved.
This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.