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MEKK1 Associated with Neuronal Apoptosis Following Intracerebral Hemorrhage

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Abstract

The JNKs have been implicated in a variety of biological functions in mammalian cells, including apoptosis and the responses to stress. However, the physiological role of these pathways in the intracerebral hemorrhage (ICH) has not been fully elucidated. In this study, we identified a MAPK kinase kinase (MAPKKK), MEKK1, may be involved in neuronal apoptosis in the processes of ICH through the activation of JNKs. From the results of western blot, immunohistochemistry and immunofluorescence, we obtained a significant up-regulation of MEKK1 in neurons adjacent to the hematoma following ICH. Increasing MEKK1 level was found to be accompanied with the up-regulation of p-JNK 3, p53, and c-jun. Besides, MEKK1 co-localized well with p-JNK in neurons, indicating its potential role in neuronal apoptosis. What’s more, our in vitro study, using MEKK1 siRNA interference in PC12 cells, further confirmed that MEKK1 might exert its pro-apoptotic function on neuronal apoptosis through extrinsic pathway. Thus, MEKK1 may play a role in promoting the brain damage following ICH.

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Acknowledgements

The funding was provided by Natural Science Foundation of China (Grant No. 81202368, 81371299). The Colleges and Universities in Natural Science Research Project of Jiangsu Province (13KJB310009); A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD); Technology Innovation Programme of Jiangsu province (No. CXLX13_876); Technology Innovation Programme of Nantong University (Nos. YKC13075, YKC13086).

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    Authors and Affiliations

    1. Department of Rehabilitation, The Second Peoples Hospital of Nantong, Affiliated of Nantong University, Nantong, 226001, Jiangsu Province, China

      Hongjian Lu, Xuelei Tao, Jianbing Ren, **njian Song, Weidong Tao & Jianbin Yang

    2. Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China

      **ao** Ning, Liang Zhu, Lijian Han & Tao Tao

    3. Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, 226001, Jiangsu Province, China

      **ao** Ning, Liang Zhu, Lijian Han & Tao Tao

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    Hongjian Lu and **ao** Ning have contributed equally to this work.

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    Lu, H., Ning, X., Tao, X. et al. MEKK1 Associated with Neuronal Apoptosis Following Intracerebral Hemorrhage. Neurochem Res 41, 3308–3321 (2016). https://doi.org/10.1007/s11064-016-2063-1

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