Increased phosphorylation of neurogranin in the brain of hypoxic preconditioned mice.
Neurogranin/RC3 (Ng/rodent cortex-enriched mRNA clone #3), a postsynaptic neuronal protein kinase C (PKC) substrate, binds calmodulin (CaM) at low Ca(2+) levels. Neurotransmitters triggering influx calcium induce neurogranin phosphorylation by PKC in physiological or pathophysiological conditions. Phosphorylated Ng reduces the affinity of Ng to bind CaM, which may affect the activities of calmodulin-dependent downstream enzymes, such as nitric oxide synthase (NOS), CaM-dependent protein kinase II (CaMKII) and adenylate cyclase (AC). These protein enzymes have been reported to play key roles in the development of ischemic/hypoxic preconditioning (I/HPC). We previously demonstrated that activation of cPKCbetaII and gamma isoforms may be involved in the early phase of cerebral hypoxic preconditioning. However, as a substrate of PKC, the role of Ng in the onset of cerebral hypoxic preconditioning is unknown. In this study, we examined the effects of repetitive hypoxic exposure on the status of Ng phosphorylation in the cortex and hippocampus of mice. Using Western blot analysis, we found that the levels of Ng phosphorylation in the cortex and hippocampus of the hypoxic group of mice increased significantly from that of the normoxic group (p<0.05). These results suggest that neurogranin protein may be involved in the development of cerebral hypoxic preconditioning.
Li
Junfa
J
Institute for Biomedical Science of Pain, Beijing Key Laboratory for Neural Regeneration and Repairing, Department of Neurobiology, Capital University of Medical Sciences, Beijing 100054, China. junfali@cpums.edu.cn
Yang
Cailian
C
Han
Song
S
Zu
Pengyu
P
Wu
Jing
J
Xu
Qunyuan
Q
Fang
Li
L
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051579:Neurogranin / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*
D051579:Neurogranin; D011493:Protein Kinase C