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Cytosolic HMGB1 Mediates Autophagy Activation in an Emulsified Isoflurane Anesthesia Cell Model

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Abstract

Inhalation anesthetic isoflurane may cause an increased risk of cognitive impairment. Previous studies have indicated that this cognitive decline is associated with neuroinflammation mediated by high mobility group box 1 (HMGB1). HMGB1 is released from cells and acts as a damage-associated molecule in neurodegenerative diseases. However, the effect of intracellular HMGB1 during emulsified isoflurane (EI) exposure is poorly understood. The purpose of this study was to investigate the effect of autophagy on neuroprotection, evaluate variation of HMGB1, and determine its role in autophagic flux after EI exposure in vitro. We observed that EI decreased cell viability in a concentration-dependent manner, accompanied by an increase in autophagic flux. EI exposure also elevates the HMGB1 level in cytoplasm. Further, cytosolic HMGB1 was necessary for autophagy by perturbing the beclin1-Bcl-2 interaction. Most importantly, autophagy induction by rapamycin alleviated EI-provoked cell injury, and HMGB1 knockdown induced autophagy inhibition, which exacerbated cell damage. Based on these findings, we propose that autophagic flux is sustained and upregulated in response to EI exposure by increased cytosolic HMGB1, and that autophagy activation serves as a protective mechanism against EI-induced cytotoxicity. Thus, the complex roles of HMGB1 make it pivotal in reducing EI-induced neuronal damage.

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Acknowledgements

We would like to thank Dr. Shumei Ma at Jilin University for helping with experimental platform. We would like to thank Editage (http://www.editage.com) for English language editing.

Funding

This work was supported by Natural Science Foundation of Jilin Province (Grant No. 3T1158303430). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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  1. Department of Anesthesiology, China-Japan Union Hospital of Jilin University, No.126, Xiantai Rd, Changchun, 130000, China

    Rui-zhu Liu, Tao Li & Guo-qing Zhao

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  1. Rui-zhu Liu
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  2. Tao Li
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Correspondence to Guo-qing Zhao.

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Liu, Rz., Li, T. & Zhao, Gq. Cytosolic HMGB1 Mediates Autophagy Activation in an Emulsified Isoflurane Anesthesia Cell Model. Neurochem Res 44, 1090–1100 (2019). https://doi.org/10.1007/s11064-019-02740-5

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