| Title |
Lead Neurotoxicity on Human Neuroblastoma Cell Line SH-SY5Y is Mediated via Transcription Factor EGR1/Zif268 Induced Disrupted in Scherophernia-1 Activation
|
|---|---|
| Published in |
Neurochemical Research, June 2018
|
| DOI | 10.1007/s11064-018-2539-2 |
| Pubmed ID | |
| Authors |
Yuanyuan You, Bo Peng, Songbin Ben, Weijian Hou, Liguang Sun, Wei Jiang |
| 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. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 16 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 3 | 19% |
| Student > Ph. D. Student | 3 | 19% |
| Unspecified | 1 | 6% |
| Student > Bachelor | 1 | 6% |
| Student > Master | 1 | 6% |
| Other | 0 | 0% |
| Unknown | 7 | 44% |
| Readers by discipline | Count | As % |
|---|---|---|
| Environmental Science | 2 | 13% |
| Biochemistry, Genetics and Molecular Biology | 2 | 13% |
| Unspecified | 1 | 6% |
| Agricultural and Biological Sciences | 1 | 6% |
| Medicine and Dentistry | 1 | 6% |
| Other | 1 | 6% |
| Unknown | 8 | 50% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 06 June 2018.
All research outputs
#20,520,426
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Outputs from Neurochemical Research
#1,706
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Outputs of similar age
#289,413
of 329,877 outputs
Outputs of similar age from Neurochemical Research
#14
of 26 outputs
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