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- Izumi Yasuhiko
- Lab. Pharmacol., Kobe Pharm. Univ.
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- Uegomori Momoko
- Lab. Pharmacol., Kobe Pharm. Univ.
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- Kobayashi Fumika
- Lab. Pharmacol., Kobe Pharm. Univ.
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- Koya Yamaki Koya
- Lab. Pharmacol., Kobe Pharm. Univ.
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- Kume Toshiaki
- Dept. Appl. Pharmacol, Grad. Sch. of Med. and Pharm. Sci., Univ. of Toyama
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- Koyama Yutaka
- Lab. Pharmacol., Kobe Pharm. Univ.
Bibliographic Information
- Other Title
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- Nrf2活性化薬の抗炎症作用にNrf2遺伝子が関与しない可能性
Abstract
<p>The Keap1-Nrf2-ARE pathway regulates the expression of phase II detoxifying enzymes and antioxidant enzymes. Nrf2 activators have been reported to have anti-inflammatory effects, although the detailed mechanisms are unknown. In this study, we investigated whether the transcription factor Nrf2 is involved in the suppression of microglial activation by the Nrf2 activator TPNA10168 as well as the multiple sclerosis therapeutic agent dimethyl fumarate. Mutations were introduced into the Nrf2 gene using the Crisper-Cas9 system in mouse-derived microglial cell line BV2 cells. Nrf2 protein was not detected in normal BV2 cells, but was accumulated by treatment with the proteasome inhibitor MG132. However, in BV2 cells in which a mutation was introduced into the Nrf2 gene, the Nrf2 protein could not be detected even after treatment with MG132, confirming that the Nrf2 gene was knocked out. Phase II detoxifying enzymes and antioxidant proteins elevated by treatment with TPNA10168 were suppressed in Nrf2 knockout cells. On the other hand, the inhibitory effects of TPNA10168 and dimethyl fumarate on induction of inflammatory cytokine mRNA by interferon-γ was not suppressed in Nrf2 knockout cells. These results suggest that Nrf2 is not involved in the anti-inflammatory mechanism of TPNA10168 and dimethyl fumarate.</p>
Journal
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- Proceedings for Annual Meeting of The Japanese Pharmacological Society
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Proceedings for Annual Meeting of The Japanese Pharmacological Society 94 (0), 2-P1-LB47-, 2021
Japanese Pharmacological Society
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Details 詳細情報について
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- CRID
- 1390568916164470272
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- NII Article ID
- 130008001391
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- ISSN
- 24354953
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- Text Lang
- ja
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- Data Source
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- JaLC
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed