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- 田島 雅道
- 明海大・歯・薬理
書誌事項
- タイトル別名
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- Bisphosphonate induces the mitophagy of osteoblastic cells by forming the chelate with intracellular metal ions
抄録
<p>Extracting teeth of patients treated with bisphosphonate (BP) occasionally induces the necrosis of jaw, but the cause of disease is still unclear. I have proved that the BPs taken into osteoblastic cells were gradually accumulated in lysosomes. In the present study, I investigated the mechanism of BP-induced cytotoxicity in osteoblast, focusing on mitochondria. MC3T3-E1 cells were used as osteoblastic cells. The uptake of BP into cells was observed by fluorescent BP. The intracellular reactive oxygenspecies (ROS) were evaluated by CM-H2-DCFDA. Detection of autophagy and mitophagy was used DALGreen and mtphagy dye, respectively. The intracellular Ca2+ and mitochondrial Fe2+ were measured by Fluo 4-AM and Mito-FerroGreen, respectively. Zoledronate (ZD) impaired cells dose-dependently. BP taken into cells was accumulated into lysosomes. MC3T3-E1 cells were always occurred autophagy flux, but bafilomycin A1(BM), a lysosome inhibitor induced cell death, by inhibiting autophagy flux. ZD slightly suppressed the autophagy flux, however the combination of BM and ZD strongly enhanced cell death. ZD decreased intracellular Ca2+and mitochondrial Fe2+, and inhibited the response of intracellular ROS generation by oxidative stress, resulting in promotion of mitophagy. These results suggest that BP may form the chelate with Ca2+and Fe2+, and promote mitophagy of damaged mitochondria. Furthermore, the accumulation of BP into lysosomes indicates to induce cell death by inhibiting the autophagy flux.</p>
収録刊行物
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- 日本薬理学会年会要旨集
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日本薬理学会年会要旨集 93 (0), 3-P-377-, 2020
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
- 1390283659860137728
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- NII論文ID
- 130007811942
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- ISSN
- 24354953
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
- Crossref
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可