title: Cell type-specific activation of p38 MAPK in the brain regions of hypoxic preconditioned mice.
abstract: Activation of p38 mitogen-activated protein kinase (p38 MAPK) has been implicated as a mechanism of ischemia/hypoxia-induced cerebral injury. The current study was designed to explore the involvement of p38 MAPK in the development of cerebral hypoxic preconditioning (HPC) by observing the changes in dual phosphorylation (p-p38 MAPK) at threonine180 and tyrosine182 sites, protein expression, and cellular distribution of p-p38 MAPK in the brain of HPC mice. We found that the p-p38 MAPK levels, not protein expression, increased significantly (p<0.05) in the regions of frontal cortex, hippocampus, and hypothalamus of mice in response to repetitive hypoxic exposure (H1-H6, n=6 for each group) when compared to values of the control normoxic group (H0, n=6) using Western blot analysis. Similar results were also confirmed by an immunostaining study of the p-p38 MAPK location in the frontal cortex, hippocampus, and hypothalamus of mice from HPC groups. To further define the cell type of p-p38 MAPK positive cells, we used a double-labeled immunofluorescent staining method to co-localize p-p38 MAPK with neurofilaments heavy chain (NF-H, neuron-specific marker), S100 (astrocyte-specific marker), and CD11b (microglia-specific maker), respectively. We found that the increased p-p38 MAPK occurred in microglia of cortex and hippocampus, as well as in neurons of hypothalamus of HPC mice. These results suggest that the cell type-specific activation of p38 MAPK in the specific brain regions might contribute to the development of cerebral HPC mechanism in mice.
authors.affiliation: Institute for Biomedical Science of Pain, Beijing Key Laboratory for Neural Regeneration and Repairing, Department of Neurobiology, Capital Medical University, #10 You An Men Wai Xi Tou Tiao, Beijing 100069, China.
authors.forename: Xiangning
authors.initials: X
authors.lastname: Bu
authors.forename: Ping
authors.initials: P
authors.lastname: Huang
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Qi
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Song
authors.initials: S
authors.lastname: Han
authors.forename: Li
authors.initials: L
authors.lastname: Fang
authors.forename: Junfa
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000033:anatomy & histology / Q000201:enzymology* / Q000503:physiopathology; D018845:CD11 Antigens / Q000378:metabolism; D004789:Enzyme Activation; D005455:Fluorescent Antibody Technique; D020925:Hypoxia-Ischemia, Brain / Q000201:enzymology* / Q000503:physiopathology; D019194:Ischemic Preconditioning; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D009457:Neuroglia / Q000201:enzymology*; D009474:Neurons / Q000201:enzymology*; D010766:Phosphorylation; D009418:S100 Proteins / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018845:CD11 Antigens; D016900:Neurofilament Proteins; D009418:S100 Proteins; C051774:neurofilament protein H; D048051:p38 Mitogen-Activated Protein Kinases