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TNF-α Mediates the Intrinsic and Extrinsic Pathway in Propofol-Induced Neuronal Apoptosis Via PI3K/Akt Signaling Pathway in Rat Prefrontal Cortical Neurons

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Abstract

Propofol can cause developing neuronal apoptosis in both in vivo and in vitro studies, and the mechanism is unclear till now. Our previous study has demonstrated that propofol can increase the TNF-α expression in the prefrontal cortex in rat developing brain, the TNF-α antagonist, etanercept, can inhibit propofol-induced neuronal apoptosis, but little is known about how TNF-α mediates that process. This study reveals that propofol at clinically relevant concentrations increases the TNF-α synthesis and release in neurons, and induces neuronal apoptosis; etanercept significantly reduces neuronal apoptosis, the elevation of cleaved caspase-8 and cleaved caspase-9, or the Akt phosphorylation induced by propofol, while the selective PI3K antagonist blocks the neuroprotection of etanercept. Propofol does not change the expression of P2X7 receptor in neurons, and the P2X7 receptor antagonist cannot affect the TNF-α synthesis or release after propofol treatment. These results suggest that propofol can increase the synthesis and release of TNF-α in the primary cultured prefrontal cortical neurons, TNF-α contributes to the intrinsic and extrinsic pathway in propofol-induced neuronal apoptosis via PI3K/Akt signaling pathway, and P2X7R is not involved in the synthesis and release of TNF-α induced by propofol.

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Acknowledgements

This study was supported by the Natural Science Foundation Project of CQ (cstc2016jcyjA0050). We would like to thank Lixue Chen, Guangcheng Qing, and Xiaoyun Dou for technical assistance.

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Author notes

  1. Xiaoyuan Deng and Bo Chen are co-first authors, they contributed equally to the work.

Authors and Affiliations

  1. Department of Anesthesiology, Chongqing Cancer Institute, Chongqing, 40030, People’s Republic of China

    Xiaoyuan Deng, Bo Chen, Junfang Zhang & Hongliang Liu

  2. Institute of Life Science, Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Bin Wang

  3. Department of Anesthesiology, Chongqing Cancer Institute, No.181 Hanyu Road, Shapingba District, Chongqing, 400030, People’s Republic of China

    Hongliang Liu

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  1. Xiaoyuan Deng
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Correspondence to Hongliang Liu.

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Deng, X., Chen, B., Wang, B. et al. TNF-α Mediates the Intrinsic and Extrinsic Pathway in Propofol-Induced Neuronal Apoptosis Via PI3K/Akt Signaling Pathway in Rat Prefrontal Cortical Neurons. Neurotox Res 32, 409–419 (2017). https://doi.org/10.1007/s12640-017-9751-8

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