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Ginkgolide B Protects Neurons from Ischemic Injury by Inhibiting the Expression of RTP801

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Abstract

RTP801 (also known as REDD1), a stress-related protein, is induced by several environmental stresses such as ischemia and cigarette smoke. Although ischemia can dramatically up-regulate RTP801 expression in brain ischemia, up to now, the exact relation between RTP801 and neuronal death in ischemia is poorly understood. In the current study, using oxygen and glucose deprivation as an in vitro ischemic model in primary cultured cortical neurons, we found that the expression of RTP801 increased progressively with prolongation of ischemic duration, in which the expression of RTP801 is positively correlated with the release of lactate dehydrogenase (LDH) in neurons, and knockdown of RTP801 promoted neuronal survival in ischemia–reperfusion. It was further found that ginkgolide B (GB) could significantly increase cell viability and decrease LDH release, and at the same time reduce the levels of RTP801 mRNA and protein in neurons after ischemia and reperfusion. Moreover, GB-induced reduction in expression of RTP801 was blocked by application of LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K). These results demonstrate that RTP801 could play a detrimental role on neurons in ischemia, and GB might protect neurons against ischemic injury by inhibiting RTP801 expression via PI3K pathway.

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Abbreviations

GB:

Ginkgolide B

I/R:

Ischemia–Reperfusion

LDH:

Lactate dehydrogenase

LY:

LY294002

MTT:

3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolinum bromide

OGD:

Oxygen and glucose deprivation

PI3K:

Phosphatidylinositol 3-kinase

REDD1:

Regulated in development and DNA damage responses

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (31171143), National Basic Research Program of China (973 Program, 2011CB510004), Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), Doctoral Initial Foundation of Nantong University, Neural Regeneration Co-innovation Center of Jiangsu Province, Science and Technology Project of Nantong (HS2012037), and Natural Science Foundation of Jiangsu Higher Education Institutions (12KJB310008).

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The authors state no conflict of interest.

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Authors and Affiliations

  1. Department of Neurochemistry, Institute for Nautical Medicine, Nantong University, 9 Seyuan Road, Nantong, 226019, China

    Xiaomei Wu, Lei Chen, Baodong Ma & Li Zhu

  2. Medical Laboratory Center, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, China

    Jianyou Su

  3. Department of Neurology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, China

    Xiaosu Gu

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  1. Xiaomei Wu
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Correspondence to Li Zhu.

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Wu, X., Su, J., Chen, L. et al. Ginkgolide B Protects Neurons from Ischemic Injury by Inhibiting the Expression of RTP801. Cell Mol Neurobiol 35, 943–952 (2015). https://doi.org/10.1007/s10571-015-0189-3

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