title: Enhanced phosphorylation of cyclic AMP response element binding protein in the brain of mice following repetitive hypoxic exposure.
abstract: Cerebral ischemic/hypoxic preconditioning (I/HPC) is a phenomenon of endogenous protection that renders the brain tolerant to sustained ischemia/hypoxia. This profound protection induced by I/HPC makes it an attractive target for developing potential clinical therapeutic approaches. However, the molecular mechanism of I/HPC is unclear. Cyclic AMP (cAMP) response element binding protein (CREB), a selective nuclear transcriptional factor, plays a key role in the neuronal functions. Phosphorylation of CREB on Ser-133 may facilitate its transcriptional activity in response to various stresses. In the current study, we observed the changes in CREB phosphorylation (Ser-133) and protein expression in the brain of auto-hypoxia-induced HPC mice by using Western blot analysis. We found that the levels of phosphorylated CREB (Ser-133), but not protein expression of CREB, increased significantly (p<0.05) in the hippocampus and the frontal cortex of mice after repetitive hypoxic exposure (H2-H4, n=6 for each group), when compared to that of the normoxic (H0, n=6) or hypoxic exposure once group (H1, n=6). In addition, a significant enhancement (p<0.05) of CREB phosphorylation (Ser-133) could also be found in the nuclear extracts from the whole hippocampus of hypoxic preconditioned mice (H2-H4, n=6 for each group). These results suggest that the phosphorylation of CREB might be involved in the development of cerebral hypoxic preconditioning.
authors.affiliation: 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.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Gao
authors.forename: Ge
authors.initials: G
authors.lastname: Gao
authors.forename: Caixia
authors.initials: C
authors.lastname: Long
authors.forename: Song
authors.initials: S
authors.lastname: Han
authors.forename: Pengyu
authors.initials: P
authors.lastname: Zu
authors.forename: Li
authors.initials: L
authors.lastname: Fang
authors.forename: Junfa
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005625:Frontal Lobe / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D010766:Phosphorylation; D013997:Time Factors
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein