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Thrombin Preconditioning Attenuates Iron-Induced Neuronal Death

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Intracerebral Hemorrhage Research

Part of the book series: Acta Neurochirurgica Supplementum ((NEUROCHIRURGICA,volume 111))

Abstract

Pretreatment with a low dose of thrombin attenuated brain injury after intracerebral hemorrhage (ICH) or cerebral ischemia. This phenomenon has been called thrombin preconditioning (TPC). The current study investigated whether or not TPC reduces neuronal death induced by iron in cultured neurons. The roles of protease-activated receptors (PARs) and the p44/42 mitogen-activated protein kinase (p44/42MAPK)/70-kDa ribosomal protein S6 kinase (p70S6K) signal transduction pathway in TPC were also examined. This study had three parts: (1) primary cultured neurons were pretreated with vehicle, thrombin or PAR agonists. Cell death was induced by ferrous iron (500 μM) 24 h later. After 48 h, culture medium was collected for lactate dehydrogenase measurement; (2)neurons were treated with vehicle, thrombin or thrombin plus PPACK (D-Phe-Pro-Arg chloromethylketone) thrombin and were collected for Western blotting; (3)the effect PD098059 on TPC was examined. Cells were treated with 20 μM PD098059 or vehicle 1 h before TPC. Neuron viability was measured 24 h following exposure to ferrous iron. Preconditioning with thrombin or PAR agonists reduced iron-induced neuronal death (p < 0.05). Thrombin, but not PPACK thrombin, upregulated the protein levels of activated p44/42 MAPK and p70 S6K (p < 0.05) in neurons. PD098059 also abolished the TPC-induced neuronal protection against iron (p < 0.05). In conclusion, the protective effect of thrombin preconditioning is partially achieved through activating PARs and the p44/42 MAPK/p70S6K signal transduction pathway.

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Acknowledgment

This study was supported by grants NS-017760, NS-039866 and NS-057539 from the National Institutes of Health (NIH) and 0840016N from the American Heart Association (AHA). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH and AHA.

Conflict of interest statement We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA

    Haitao Hu, Shiro Yamashita, Shuijiang Song, Ya Hua & Richard F. Keep

  2. Department of Neurology, 2nd Affiliated Hospital, Zhejiang University, Zhejiang, China

    Haitao Hu & Shuijiang Song

  3. Department of Neurosurgery, University of Michigan, Room 5018 Biomedical Science Research Building, 109 Zina Pitcher Place, Ann Arbor, MI, USA

    Guohua Xi

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  1. Haitao Hu
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  2. Shiro Yamashita
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  3. Shuijiang Song
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  4. Ya Hua
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  5. Richard F. Keep
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  6. Guohua Xi
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Correspondence to Guohua Xi .

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Editors and Affiliations

  1. , Neurosurgery, Physiology, Loma Linda University, Campus Street 11041, Loma Linda, 92530, USA

    John Zhang

  2. School of Medicine, Dept. Neurosurgery, Loma Linda University, Anderson St. 11234, Loma Linda, 92354, California, USA

    Austin Colohan

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Hu, H., Yamashita, S., Song, S., Hua, Y., Keep, R.F., Xi, G. (2011). Thrombin Preconditioning Attenuates Iron-Induced Neuronal Death. In: Zhang, J., Colohan, A. (eds) Intracerebral Hemorrhage Research. Acta Neurochirurgica Supplementum, vol 111. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0693-8_43

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  • DOI: https://doi.org/10.1007/978-3-7091-0693-8_43

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  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-7091-0692-1

  • Online ISBN: 978-3-7091-0693-8

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