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Biglycan protects human neuroblastoma cells from nitric oxide-induced death by inhibiting AMPK-mTOR mediated autophagy and intracellular ROS level

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Abstract

The ubiquitous proteoglycan, biglycan (BGN) acts as an important modulator, regulating key molecular pathways of metabolism and brain function. Autophagy is documented as a defining feature of neurodegeneration in Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). In the present study, we found that BGN protected neuronal cells from nitric oxide (NO)-induced cell apoptosis. However, it is still unclear that whether the neuroprotective effect of BGN relates to autophagy. Here, we discovered that an NO donor, sodium nitroprusside (SNP) induced autophagy in human SH-SY5Y neuroblastoma cells, including activating LC3B and inhibiting p62. Inhibiting autophagy by 3MA aggravated NO-induced cell death, otherwise promoting autophagy by Rapamycin rescued NO-triggered cell death. Notably, BGN downregulated by NO, significantly protected SH-SY5Y cells against NO-induced neurotoxicity by inhibiting the activation of autophagy-dependent AMPK signaling pathway. Moreover, BGN overexpression also diminished NO-induced the elevation of intracellular reactive oxygen species (ROS) level, but not NO content. These findings suggest that BGN protects neuroblastoma cells from NO-induced death by suppressing autophagy-dependent AMPK-mTOR signaling and intracellular ROS level.

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Acknowledgments

This work was supported by the grants from National Natural Science Foundation of China (No. 31401181, 81771336, U1704186).

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Correspondence to Sujuan Chen.

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Chen, S., Guo, D., Lei, B. et al. Biglycan protects human neuroblastoma cells from nitric oxide-induced death by inhibiting AMPK-mTOR mediated autophagy and intracellular ROS level. Biotechnol Lett 42, 657–668 (2020). https://doi.org/10.1007/s10529-020-02818-z

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