Clioquinol Increases the Expression of VGF, a Neuropeptide Precursor, Through Induction of c-Fos Expression
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- Katsuyama Masato
- Radioisotope Center, Kyoto Prefectural University of Medicine, Japan Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan
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- Ibi Masakazu
- Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan
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- Matsumoto Misaki
- Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan
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- Iwata Kazumi
- Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan
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- Ohshima Yoichi
- Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan
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- Yabe-Nishimura Chihiro
- Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan
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Clioquinol was used extensively in the mid-1900s as an amebicide to treat indigestion and diarrhea. It was eventually withdrawn from the market because it was linked to subacute myelo-optic neuropathy (SMON) in Japan. However, the pathogenesis of SMON has not yet been elucidated in detail. As reported previously, we performed a global analysis on human neuroblastoma cells using DNA chips. The global analysis and quantitative PCR demonstrated that the mRNA level of VGF (nonacronymic), the precursor of neuropeptides involved in pain reactions, was significantly increased when SH-SY5Y and IMR-32 neuroblastoma cells were treated with clioquinol. Promoter analyses in SH-SY5Y cells revealed that a region responsive to clioquinol exists between −1381 and −1349 of the human VGF gene, which contains an activator protein (AP)-1 site–like sequence. The introduction of mutations at this site significantly reduced clioquinol-induced transcriptional activation. Clioquinol induced the expression of the AP-1 family transcription factors, c-Jun and c-Fos. Electrophoresis mobility shift assays demonstrated that c-Jun and c-Fos could bind to the AP-1 site at −1374/−1368 in SH-SY5Y cells treated with clioquinol. RNA interference against c-Fos significantly suppressed clioquinol-induced VGF mRNA expression. These results suggest that the clioquinol-induced expression of c-Fos mediates the induction of VGF expression.
収録刊行物
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 124 (4), 427-432, 2014
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390001205178481792
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- NII論文ID
- 130003391513
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- NII書誌ID
- AA11806667
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- COI
- 1:STN:280:DC%2BC2crlsFWqtA%3D%3D
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- ISSN
- 13478648
- 13478613
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- NDL書誌ID
- 025428225
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- PubMed
- 24646654
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- 使用不可