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Anti-oxidation and Antiapoptotic Effects of Chondroitin Sulfate on 6-Hydroxydopamine-Induced Injury Through the Up-Regulation of Nrf2 and Inhibition of Mitochondria-Mediated Pathway

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Abstract

The purpose of the study was to investigate the protective effect and molecular mechanism of chondroitin sulfate (CS) against 6-hydroxydopamine (6-OHDA) induced toxicity in the human neuroblastoma cell line SH-SY5Y. The results showed that CS could protect SH-SY5Y cells against 6-OHDA-induced injury. The subsequent mechanism study showed that the anti-oxidation of CS may partly be mediated through inhibiting the intracellular reactive oxygen species overproduction, recovering the reduction of nuclear NF-E2-related factor-2 (Nrf2) expression and the reduction of antioxidants activity induced by 6-OHDA. Furthermore, CS pretreatment significantly attenuated 6-OHDA-induced cell apoptosis and nuclear condensation. 6-OHDA-induced dysfunctions, including the decrease of mitochondrial membrane potential (ΔΨm), increase of intracellular free Ca2+, imbalance of Bcl-2/Bax ratio, release of Cyt-c from the mitochondria and activation of caspase-3 and caspase-9 were attenuated by CS pretreatment, which demonstrated that CS suppressed 6-OHDA-induced apoptosis in SH-SY5Y cells possibly through mitochondria protection. These results suggest that CS exhibits anti-oxidation through the up-regulation of Nrf2 along with endogenous antioxidant, and reduces apoptosis via inhibiting the mitochondrial pathway to protect SH-SY5Y cells damaged by 6-OHDA.

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Acknowledgments

The research is supported by National Natural Science Fund (No. 81441094), Natural Science Foundation of Shandong Province (No. ZR2013HQ010), Medical Scientific Foundation of Shandong Province (No. 2013WS0256), Qingdao Municipal Science and Technology Foundation (13-1-3-48-nsh), National Postdoctoral Research Project (2015M571999), Qingdao Postdoctoral Research Project and Young Foundation of Qingdao University.

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Authors and Affiliations

  1. Medical College of Qingdao University, Qingdao, 266021, Shandong, China

    Chuanxia Ju, Lin Hou, Li Zhang, Zheng Zhang, Hua Gao, Lei Wang, Dachao Wang, Yuqiang Lv & Xiaodan Zhao

  2. Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Qingdao, 266071, China

    Chuanxia Ju & Lin Hou

  3. Qingdao Municipal Hospital, Qingdao, 266011, Shandong, China

    Fusheng Sun

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  1. Chuanxia Ju
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  2. Lin Hou
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  3. Fusheng Sun
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  4. Li Zhang
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  10. Xiaodan Zhao
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Correspondence to Lin Hou.

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Ju, C., Hou, L., Sun, F. et al. Anti-oxidation and Antiapoptotic Effects of Chondroitin Sulfate on 6-Hydroxydopamine-Induced Injury Through the Up-Regulation of Nrf2 and Inhibition of Mitochondria-Mediated Pathway. Neurochem Res 40, 1509–1519 (2015). https://doi.org/10.1007/s11064-015-1628-8

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  • DOI: https://doi.org/10.1007/s11064-015-1628-8

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