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Neurochemical Research

, Volume 43, Issue 7, pp 1308–1316 | Cite as

Lead Neurotoxicity on Human Neuroblastoma Cell Line SH-SY5Y is Mediated via Transcription Factor EGR1/Zif268 Induced Disrupted in Scherophernia-1 Activation

  • Yuanyuan You
  • Bo Peng
  • Songbin Ben
  • Weijian Hou
  • Liguang SunEmail author
  • Wei Jiang
Original Paper

Abstract

Lead (Pb2+) is a well-known type of neurotoxin and chronic exposure to Pb2+ induces cognition dysfunction. In this work, the potential role of early growth response gene 1 (EGR1) in the linkage of Pb2+ exposure and disrupted in scherophernia-1 (DISC1) activity was investigated. Human neuroblastoma cell line SH-SY5Y was subjected to different concentrations of lead acetate (PbAc) to determine the effect of Pb2+ exposure on the cell viability, apoptosis, and activity of EGR1 and DISC1. Then the expression of EGR1 in SH-SY5Y cells was knocked down with specific siRNA to assess the function of EGR1 in Pb2+ induced activation of DISC1. The interaction between EGR1 and DISC1 was further validated with dual luciferase assay, Supershift electrophoretic mobility shift assay (EMSA), and chromatin immunoprecipitation (ChIP)-PCR. Administration of PbAc decreased cell viability and induced apoptosis in SH-SY5Y cells in a dose-dependent manner. Additionally, exposure to PbAc also up-regulated expression of EGR1 and DISC1 at all concentrations. Knockdown of EGR1 blocked the effect of PbAc on SH-SY5Y cells, indicating the central role of EGR1 in the function of Pb2+ on activity of DISC1. Based on the results of dual luciferase assay, Supershift EMSA, and ChIP-PCR, EGR1 mediated the effect of Pb2+ on DISC1 by directly bound to the promoter region of DISC1 gene. The current study elaborated the mechanism involved in the effect of Pb2+ exposure on expression of DISC1 for the first time: EGR1 activated by Pb2+ substitution of zinc triggered the transcription of DISC1 gene by directly binding to its promoter.

Keywords

Disrupted in scherophernia-1 Early growth response gene 1 Lead injury Neurotoxicity Promoter 

Notes

Authors’ Contribution

SBB provided the predictive information; YYY and BP designed and conducted the experiments, YYY and SBB collected the data, WJH and WJ provided instruction during experiments; YYY and LGS analysis data separately; YYY completed the draft of manuscript; LGS revised manuscript draft; all authors confirmed the version before submitting.

Compliance with Ethical Standards

Conflict of interest

Authors declared no conflict of interest.

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Copyright information

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

Authors and Affiliations

  • Yuanyuan You
    • 1
  • Bo Peng
    • 2
  • Songbin Ben
    • 3
  • Weijian Hou
    • 4
  • Liguang Sun
    • 5
    Email author
  • Wei Jiang
    • 6
  1. 1.Department of GeneticShenyang Maternity and Child Health HospitalShenyangPeople’s Republic of China
  2. 2.Outpatient DepartmentChina Medical UniversityShenyangPeople’s Republic of China
  3. 3.Life Science CollegeLiaoning UniversityShenyangPeople’s Republic of China
  4. 4.Department of Tissue EngineeringChina Medical UniversityShenyangPeople’s Republic of China
  5. 5.Department of Biochemical and Molecular BiologyChina Medical UniversityShenyangPeople’s Republic of China
  6. 6.Department of Biological ScienceLiaoning Academy of Analytical SciencesShenyangPeople’s Republic of China

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