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Erythropoietin prevents PC12 cells from 1-methyl-4-phenylpyridinium ion-induced apoptosis via the Akt/GSK-3β/caspase-3 mediated signaling pathway

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Abstract

Apoptosis is a contributing cause of dopaminergic neuron loss in Parkinson disease. Recent work has shown that erythropoietin (EPO) offers protection against apoptosis in a wide variety of tissues. We demonstrate that exposure of PC12 cells to 1-methyl-4-phenylpyridinium ion (MPP+) with recombinant human EPO, significantly decreased apoptosis as measured by TUNEL and caspase-3 activity when compared to MPP+ treatment alone. EPO induced sustained phosphorylation of Akt and its substrate, GSK-3β, reduced caspase-3 activities in PC12 cells. The anti-apoptotic effect of EPO was abrogated by co-treatment with LY294002, the specific blocker of phosphatidylinositol 3-kinase (PI3K). The effects of EPO on GSK-3β and caspase-3 activities were also blocked by LY294002. LiCl, the inhibitor of GSK-3β, downregulated the caspase-3 activity and blocked the apoptosis induced by MPP+. Finally, we determined that EPO transiently activated the ERK signaling pathway, but PD98059, a specific inhibitor of ERK, does not alter the survival effect of EPO in this model system. Thus, these findings indicate that EPO protects against apoptosis in PC12 cells exposed to MPP+, through the Akt/GSK-3β/caspase-3 signaling pathway, but the ERK pathway is not involved in the EPO-dependent survival enhancing effect in this model system.

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Acknowledgements

The authors gratefully acknowledge Jieping Zhou for technical assistance. This study was supported by a grant from the Program of National Natural Science Foundation of China (No. 30570627/C030307).

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Authors and Affiliations

  1. Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Yan Wu & Shenggang Sun

  2. Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    You Shang

  3. Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Huifang Liang

  4. Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Rengang Liu

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  1. Yan Wu
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  2. You Shang
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Correspondence to Shenggang Sun.

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The authors Yan Wu and You Shang are equally contributed to this work.

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Wu, Y., Shang, Y., Sun, S. et al. Erythropoietin prevents PC12 cells from 1-methyl-4-phenylpyridinium ion-induced apoptosis via the Akt/GSK-3β/caspase-3 mediated signaling pathway. Apoptosis 12, 1365–1375 (2007). https://doi.org/10.1007/s10495-007-0065-9

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