期刊
BRAIN RESEARCH
卷 1503, 期 -, 页码 78-88出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2013.01.051
关键词
Hypoxic preconditioning; Middle cerebral artery occlusion; Phosphorylation of p38 mitogen-activated protein kinase; Bcl-xL; Apoptosis; Neuroprotection
资金
- National Natural Science Foundation of China [31071048, 31171147, 31140005]
- China 973 Pre-program [2011CB512109]
- Ph.D. Programs Foundation of Ministry of Education of China [20091107110001]
- Basic and clinical research joint program of Capital Medical University [11JL34, 11JL44]
- Research fund of Capital Medical University [2011ZR02]
- Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry
Hypoxic preconditioning (HPC) initiates intracellular signaling pathway to provide protection, but the role of p38 mitogen-activated protein kinase (p38 MAPK) in HPC-induced neuroprotection against cerebral ischemic injuries is a matter of debate. In this study, we found that HPC could reduce 6 h middle cerebral artery occlusion (MCAO)-induced infarct volume, edema ratio and cell apoptosis, as well as enhancing the up-regulated p38 MAPK phosphorylation (P-p38 MAPK) levels in the pen-infarct region of mice after 6 h MCAO. However, intracerebroventricular injection of p38 MAPK inhibitor SB203580 abolished this HPC-induced neuroprotection. HPC significantly increased the translocation of antiapoptotic Bcl-2-related protein Bcl-xL from the cytosol to the mitochondria in the peri-infarct region of MCAO mice. Interestingly, the results of reciprocal immunoprecipitation showed that Bcl-xL and P-p38 MAPK were coimmunoprecipitated reciprocally only in the pen-infarct region of HPC and MCAO treated mice, while Bcl-xL and total p38 (T-p38 MAPK), not P-p38 MAPK, could be coimmunoprecipited by each other in the brain of normal control mice. In addition, we found SB203580 significantly decreased P-p38 MAPK levels, and inhibited HPC-induced mitochondria translocation of Bcl-xL in the brain of HPC and MCAO treated mice. Taken together, our findings suggested that P-p38 MAPK mediates HPC-induced neuroprotection against cerebral ischemic injury via mitochondria translocation of Bcl-xL, which might be a key anti-cell apoptotic mechanism of HPC. (C) 2013 Elsevier B.V. All rights reserved.
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