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Lipopolysaccharide induces human olfactory ensheathing glial apoptosis by promoting mitochondrial dysfunction and activating the JNK-Bnip3-Bax pathway

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Cell Stress and Chaperones Aims and scope

Abstract

Olfactory ensheathing glia (OEG) play an important role in regulating the regeneration of an injured nervous system. However, chronic inflammation damage reduces the viability of OEG via poorly understood mechanisms. We aimed to investigate the pathological responses of OEG in response to LPS-mediated inflammation stress in vitro. The results indicated that lipopolysaccharide (LPS) treatment significantly reduced the viability of OEG in a dose-dependent fashion. Mechanistically, LPS stimuli induced mitochondrial oxidative damage, mitochondrial fragmentation, mitochondrial metabolism disruption, and mitochondrial apoptosis activation. Furthermore, we verified that LPS modulated mitochondrial apoptosis by promoting Bax upregulation, and this process was regulated by the JNK-Bnip3 pathway. Inhibition of the JNK-Bnip3 pathway prevented LPS-mediated Bax activation, thus attenuating OEG apoptosis. Altogether, our data illustrated that LPS-mediated inflammation injury evoked mitochondrial abnormalities in OEG damage via the JNK-Bnip3-Bax pathway. This finding provides a potential target to protect OEG against chronic inflammation stress.

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Funding

This study was supported by grants from the major project of logistic scientific Research of PLA (AWS14C003–5).

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MWH, ZMX, and JMC were involved in the conception and design, performance of experiments, data analysis and interpretation, and manuscript writing. LBX, YTD, FQL, and JMC were involved in data analysis and interpretation.

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Correspondence to Jianmei Chen.

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The authors declare that they have no competing interests.

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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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He, M., Xiang, Z., Xu, L. et al. Lipopolysaccharide induces human olfactory ensheathing glial apoptosis by promoting mitochondrial dysfunction and activating the JNK-Bnip3-Bax pathway. Cell Stress and Chaperones 24, 91–104 (2019). https://doi.org/10.1007/s12192-018-0945-7

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  • DOI: https://doi.org/10.1007/s12192-018-0945-7

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