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Biglycan, a Nitric Oxide-Downregulated Proteoglycan, Prevents Nitric Oxide-Induced Neuronal Cell Apoptosis via Targeting Erk1/2 and p38 Signaling Pathways

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Abstract

Nitric oxide (NO), a gaseous signaling molecule, induces apoptosis and mediates neurodegenerative diseases and brain injury. Biglycan (BGN), a member of the small leucine-rich proteoglycan family, was demonstrated to exert anti-apoptosis function in various disease models. However, little is known about the effect of BGN on NO-induced neurotoxicity. Here, for the first time, we reported that BGN protects against NO-induced apoptosis in human neuroblastoma SH-EP1 cells. This is supported by the finding that sodium nitroprusside (SNP), a NO donor, triggered downregulation of BGN in SH-EP1 cells, and over-expression of BGN strikingly attenuated NO-induced nuclear fragmentation and apoptosis of neuronal cells. More importantly, BGN remarkably blocked NO-induced phosphorylation of Erk1/2 and p38 signaling, but not JNK MAPK pathway in neuronal cells. Furthermore, inhibiting Erk1/2 by U0126 or p38 by SB203580 partially protected against NO-induced cell death. Conversely, downregulation of BGN by siRNA aggravated NO-induced neuronal cell death, which was not attenuated by U0126 or SB203580. These findings indicated that BGN, downregulated by NO, prevents NO-induced neuronal cell apoptosis via targeting Erk1/2 and p38 signaling pathways. Our results strongly suggest that BGN could be explored for the prevention of NO-induced neurodegenerative disorders.

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Funding

This study was supported by the grants from National Natural Science Foundation of China (Nos. 31401181, 81402416, 81771336, U1704186), and grants from Henan Natural Science Foundation of China (No. 182300410381).

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Authors and Affiliations

  1. Synthetic Biology Engineering Lab of Henan Province, School of Sciences and Technology, Xinxiang Medical University, Henan, China

    Sujuan Chen, Dandan Guo, Lei Wang, Rui Yang & Jiajia Bi

  2. College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, China

    Wei Zhang

  3. School of Sciences and Technology, Xinxiang Medical University, Henan, China

    Yunfei Xie, Haijie Yang & Binfeng Cheng

  4. School of Basic Medical Sciences, Xinxiang Medical University, Henan, China

    Zhiwei Feng

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  1. Sujuan Chen
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  2. Dandan Guo
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  3. Wei Zhang
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  4. Yunfei Xie
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  7. Lei Wang
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  9. Jiajia Bi
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  10. Zhiwei Feng
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Correspondence to Jiajia Bi or Zhiwei Feng.

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Electronic Supplementary Material

Fig. S1

BGN reduces the ROS accumulation induced by NO in SH-EP1 cells. Intracellular ROS level was detected by DHE staining and observed by a fluorescent microscope. The fluorescence of DHE in SNP-treated cells was much stronger than that in the negative control, implying that the ROS level was elevated by SNP. Over-expression of BGN resulted in weakened fluorescence in the SNP-treated cells, which imply that BGN partially reduced NO-induced ROS level. Scale bars: 100 μm (n = 3) (PNG 68 kb)

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Chen, S., Guo, D., Zhang, W. et al. Biglycan, a Nitric Oxide-Downregulated Proteoglycan, Prevents Nitric Oxide-Induced Neuronal Cell Apoptosis via Targeting Erk1/2 and p38 Signaling Pathways. J Mol Neurosci 66, 68–76 (2018). https://doi.org/10.1007/s12031-018-1151-x

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  • DOI: https://doi.org/10.1007/s12031-018-1151-x

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