These authors contributed equally to this study.
Proteomic analysis of cPKCβII-interacting proteins involved in HPC-induced neuroprotection against cerebral ischemia of mice
Article first published online: 1 MAR 2011
© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry
Journal of Neurochemistry
Volume 117, Issue 2, pages 346–356, April 2011
How to Cite
Bu, X., Zhang, N., Yang, X., Liu, Y., Du, J., Liang, J., Xu, Q. and Li, J. (2011), Proteomic analysis of cPKCβII-interacting proteins involved in HPC-induced neuroprotection against cerebral ischemia of mice. Journal of Neurochemistry, 117: 346–356. doi: 10.1111/j.1471-4159.2011.07209.x
- Issue published online: 1 APR 2011
- Article first published online: 1 MAR 2011
- Accepted manuscript online: 3 FEB 2011 12:00PM EST
- Received November 28, 2010; revised manuscript received/accepted January 28, 2011.
- collapsin response mediator protein-2;
- conventional protein kinase CβII;
- hypoxic preconditioning;
- middle cerebral artery occlusion;
J. Neurochem. (2011) 117, 346–356.
Hypoxic preconditioning (HPC) initiates intracellular signaling pathway to provide protection against subsequent cerebral ischemic injuries, and its mechanism may provide molecular targets for therapy in stroke. According to our study of conventional protein kinase C βII (cPKCβII) activation in HPC, the role of cPKCβII in HPC-induced neuroprotection and its interacting proteins were determined in this study. The autohypoxia-induced HPC and middle cerebral artery occlusion (MCAO)-induced cerebral ischemia mouse models were prepared as reported. We found that HPC reduced 6 h MCAO-induced neurological deficits, infarct volume, edema ratio and cell apoptosis in peri-infarct region (penumbra), but cPKCβII inhibitors Go6983 and LY333531 blocked HPC-induced neuroprotection. Proteomic analysis revealed that the expression of four proteins in cytosol and eight proteins in particulate fraction changed significantly among 49 identified cPKCβII-interacting proteins in cortex of HPC mice. In addition, HPC could inhibit the decrease of phosphorylated collapsin response mediator protein-2 (CRMP-2) level and increase of CRMP-2 breakdown product. TAT-CRMP-2 peptide, which prevents the cleavage of endogenous CRMP-2, could inhibit CRMP-2 dephosphorylation and proteolysis as well as the infarct volume of 6 h MCAO mice. This study is the first to report multiple cPKCβII-interacting proteins in HPC mouse brain and the role of cPKCβII-CRMP-2 in HPC-induced neuroprotection against early stages of ischemic injuries in mice.