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Neurotoxicity Research

, Volume 35, Issue 1, pp 139–149 | Cite as

Dexmedetomidine Protects Against Chemical Hypoxia-Induced Neurotoxicity in Differentiated PC12 Cells Via Inhibition of NADPH Oxidase 2-Mediated Oxidative Stress

  • Xiao-Hui Chen
  • Dong-Tai Chen
  • Xiong-Mei Huang
  • Yong-Hua Chen
  • Jia-Hao Pan
  • Xiao-Chun Zheng
  • Wei-An ZengEmail author
ORIGINAL ARTICLE
  • 113 Downloads

Abstract

Dexmedetomidine (Dex) is a widely used sedative in anesthesia and critical care units, and it exhibits neuroprotective activity. However, the precise mechanism of Dex-exerted neuroprotection is not clear. Increased neuronal NADPH oxidase 2 (NOX2) contributes to oxidative stress and neuronal damage in various hypoxia-related neurodegenerative disorders. The present study investigated whether Dex regulated neuronal NOX2 to exert its protective effects under hypoxic conditions. Well-differentiated PC12 cells were exposed to cobalt chloride (CoCl2) to mimic a neuronal model of chemical hypoxia-mediated neurotoxicity. The data showed that Dex pretreatment of PC12 cells significantly suppressed CoCl2-induced neurotoxicity, as evidenced by the enhanced cell viability, restoration of cellular morphology, and reduction in apoptotic cells. Dex improved mitochondrial function and inhibited CoCl2-induced mitochondrial apoptotic pathways. We further demonstrated that Dex attenuated oxidative stress, downregulated NOX2 protein expression and activity, and inhibited intracellular calcium ([Ca2+]i) overload in CoCl2-treated PC12 cells. Moreover, knockdown of the NOX2 gene markedly improved mitochondrial function and attenuated apoptosis under hypoxic conditions. These results demonstrated that the protective effects of Dex against hypoxia-induced neurotoxicity in neural cells were mediated, at least partially, via inhibition of NOX2-mediated oxidative stress.

Keywords

Dexmedetomidine Hypoxia· NADPH oxidase 2 Oxidative stress PC12 cells 

Notes

Funding Information

This study was supported by the Natural Science Foundation of China (NSFC; No. 81571076).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Xiao-Hui Chen
    • 1
    • 2
  • Dong-Tai Chen
    • 1
  • Xiong-Mei Huang
    • 3
  • Yong-Hua Chen
    • 4
  • Jia-Hao Pan
    • 1
  • Xiao-Chun Zheng
    • 2
  • Wei-An Zeng
    • 1
    Email author
  1. 1.Department of AnesthesiologySun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineGuangzhouChina
  2. 2.Department of AnesthesiologyFujian Provincial Clinical Medical College, Fujian Medical University, Fujian Provincial HospitalFuzhouChina
  3. 3.Department of Burn and Plastic SurgeryFujian Provincial Clinical Medical College, Fujian Medical University, Fujian Provincial HospitalFuzhouChina
  4. 4.Department of AnesthesiologyPeking University Shenzhen HospitalShenzhenChina

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