| First Author | Feng S | Year | 2013 |
| Journal | Neurochem Int | Volume | 63 |
| Issue | 2 | Pages | 69-79 |
| PubMed ID | 23665338 | Mgi Jnum | J:338269 |
| Mgi Id | MGI:6836987 | Doi | 10.1016/j.neuint.2013.04.011 |
| Citation | Feng S, et al. (2013) Insight into hypoxic preconditioning and ischemic injury through determination of nPKCepsilon-interacting proteins in mouse brain. Neurochem Int 63(2):69-79 |
| abstractText | Cerebral hypoxic preconditioning (HPC) provides neuroprotection by intracellular signaling pathways. We previously demonstrated that novel protein kinase Cepsilon (nPKCepsilon) activation participated in cerebral HPC development. In this study, we explore the role of nPKCepsilon in HPC-induced neuroprotection against middle cerebral artery occlusion (MCAO)-induced ischemic injury and identify its possible signaling molecules. A total of 131 adult male BALB/c mice were divided into eight groups: normoxic control (n=9), HPC (n=9), HPC+epsilonV1-2 (n=13), Sham (n=19), HPC+sham (n=6), Ischemia (I, 6h MCAO, n=31), HPC+I (n=25) and HPC+epsilonV1-2+I (n=19). nPKCepsilon specific inhibitor epsilonV1-2 was administered via intracerebroventricular injection. Western blot, 2,3,5-triphenyltetrazolium chloride staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were applied to determine nPKCepsilon membrane translocation, infarction volume and programmed cell death (PCD), respectively. Two-dimensional gel electrophoresis (2-De) and matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used to identify nPKCepsilon-interacting proteins, followed by bioinformatics analysis of genee ontology (GO) to predict nPKCepsilon-specific signaling pathways. Our results showed that HPC attenuates MCAO-induced brain injuries and stabilized nPKCepsilonmembrane translocation in peri-infarct region, which was abolished by nPKCepsilon-speecific inhibitor epsilonV1-2. Proteomics analysis revealed 8 up- and 3 down-regulated nPKCepsilon-interacting proteins both in cytosolic and particulate fractions of HPC mouse brain. GO analysis predicted 25 significant nPKCepsilon-specific signaling pathways among the 16 identified nPKCepsilon-interacting proteins in brain of HPC mice. This study is the first to report multiple nPKCepsilon-interacting proteins and their signaling pathways in HPC mouse brain, suggesting that nPKCepsilon signaling molecules is responsible for HPC-induced neuroprotection against cerebral ischemic injuries of mice. |
