Journal of Capital Medical University ›› 2013, Vol. 34 ›› Issue (6): 820-825.doi: 10.3969/j.issn.1006-7795.2013.06.008

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Effect of glucocerebrosidase inhibition on intracellular α-synuclein oligomer formation and autophagic activity of dopaminergic cells

LIU Guangwei1,2, YIN Na1,2, MI Na1,2, LI Xin1,2, LI Yaohua1,2, YU Shun1,2   

  1. 1. Department of Neurobiology, Xuanwu Hospital, Capital Medical University, Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing 100053, China;
    2. Beijing Geriatric Medical and Clinical Center, Beijing 100053, China
  • Received:2013-10-18 Online:2013-12-21 Published:2013-12-13
  • Supported by:

    This study was supported by the National Natural Science Foundation of China(81071014);National Basic Research and Development Program(973 Program) of China(2011CB504101);The National Science and Technology Support Program(2012BAI10B03);Natural Science Foundation of Beijing(7102076);The Capital Health Research and Development Project(SHOUFA 2011-1001-01).

Abstract:

Objective To investigate the effect of glucocerebrosidase (GBA) inhibition on intracellular α-synuclein(α-Syn) oligomer formation and autophagic activity of dopaminergic cells. Methods The activity of GBA was measured in MES 23.5 cells treated with different concentrations of CβE, the specific GBA inhibitor. After treatment with CβE, monomeric α-Syn was added into the medium and the amount of intracellular α-Syn oligomers were evaluated by ELISA. The autophagic activity, oxidative stress, and apoptotic cell counts were also examined. Results CβE dose-dependently decreased the activity of GBA and increased the levels of intracellular α-Syn oligomers. CβE also enhanced the autophagic activity, oxidative stress levels and apoptotic cell counts in an α-Syn concentration-dependent manner. Conclusion GBA inhibition causes intracellular accumulation of α-Syn oligomers and α-Syn concentration-dependent enhancement of autophagy, oxidative stress and apoptosis.

Key words: glucocerebrosidase, α-synuclein oligomer, MES 23.5 cells, autophagy

CLC Number: