Neuron-specific phosphorylation of c-Jun N-terminal kinase increased in the brain of hypoxic preconditioned mice.
Accumulated studies have suggested that mitogen-activated protein kinase (MAPK) play a pivotal role in the development of cerebral hypoxic preconditioning (HPC). By using our "auto-hypoxia"-induced HPC mouse model, we have reported increased phosphorylation level of p38 MAPK, and decreased phosphorylation and protein expression levels of extracellular signal regulated kinases 1/2 (ERK1/2) in the brain of HPC mice. In the current study, we investigated the involvement of c-Jun N-terminal kinase (JNK) in the brain of HPC mice. By using Western blot analysis, we found that the phosphorylation levels of JNK at Thr183 and Tyr185 sites (phospho-Thr183/Tyr185 JNK), but not its protein expression, increased significantly (p<0.05, n=6 for each group) both in the hippocampus and frontal cortex of early (H1-H4) and delayed (H5 and H6) HPC mice than that of the normoxic group (H0, n=6). Similarly, enhanced phospho-Thr183/Tyr185 JNK was also observed by immunostaining in the hippocampus and frontal cortex of mice following series of hypoxic exposures (H3 and H6). In addition, we found that phospho-Thr183/Tyr185 JNK predominantly co-localized with a neuron-specific protein, neurogranin, in both the hippocampus and frontal cortex of HPC mice (H3) by using double-labeled immunofluorescence. These results suggest that the increased neuron-specific phosphorylation of JNK at Thr183/Tyr185, not protein expression, might be involved in the development of cerebral HPC of mice.
Zhang
Nan
N
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.
Gao
Ge
G
Bu
Xiangning
X
Han
Song
S
Fang
Li
L
Li
Junfa
J
D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000378:metabolism; D005625:Frontal Lobe / Q000201:enzymology; D006624:Hippocampus / Q000201:enzymology; D002534:Hypoxia, Brain / Q000201:enzymology* / Q000378:metabolism; D007158:Immunologic Techniques; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051579:Neurogranin / Q000378:metabolism; D009474:Neurons / Q000201:enzymology*; D010766:Phosphorylation; D013194:Staining and Labeling; D013912:Threonine; D014018:Tissue Distribution; D014443:Tyrosine
D051579:Neurogranin; D013912:Threonine; D014443:Tyrosine; D048031:JNK Mitogen-Activated Protein Kinases