Reference - Detail
| RRC ID | 61420 |
|---|---|
| Author | Yamada S, Kubo Y, Yamazaki D, Sekino Y, Kanda Y. |
| Title | Chlorpyrifos inhibits neural induction via Mfn1-mediated mitochondrial dysfunction in human induced pluripotent stem cells. |
| Journal | Sci Rep |
| Abstract |
Organophosphates, such as chlorpyrifos (CPF), are widely used as insecticides in agriculture. CPF is known to induce cytotoxicity, including neurodevelopmental toxicity. However, the molecular mechanisms of CPF toxicity at early fetal stage have not been fully elucidated. In this study, we examined the mechanisms of CPF-induced cytotoxicity using human induced pluripotent stem cells (iPSCs). We found that exposure to CPF at micromolar levels decreased intracellular ATP levels. As CPF suppressed energy production that is a critical function of the mitochondria, we focused on the effects of CPF on mitochondrial dynamics. CPF induced mitochondrial fragmentation via reduction of mitochondrial fusion protein mitofusin 1 (Mfn1) in iPSCs. In addition, CPF reduced the expression of several neural differentiation marker genes in iPSCs. Moreover, knockdown of Mfn1 gene in iPSCs downregulated the expression of PAX6, a key transcription factor that regulates neurogenesis, suggesting that Mfn1 mediates neural induction in iPSCs. Taken together, these results suggest that CPF induces neurotoxicity via Mfn1-mediated mitochondrial fragmentation in iPSCs. Thus, mitochondrial dysfunction in iPSCs could be used as a possible marker for cytotoxic effects by chemicals. |
| Volume | 7 |
| Pages | 40925 |
| Published | 2017-1-23 |
| DOI | 10.1038/srep40925 |
| PII | srep40925 |
| PMID | 28112198 |
| PMC | PMC5256306 |
| MeSH | Cell Line Chlorpyrifos / toxicity* Cholinesterase Inhibitors / toxicity* GTP Phosphohydrolases / metabolism* Humans Induced Pluripotent Stem Cells / drug effects* Induced Pluripotent Stem Cells / metabolism Insecticides / toxicity* Mitochondria / metabolism* Mitochondrial Membrane Transport Proteins / metabolism* PAX6 Transcription Factor / genetics PAX6 Transcription Factor / metabolism |
| IF | 3.998 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 7 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | 253G1(HPS0002) |