Bisphosphonate induces the mitophagy of osteoblastic cells by forming the chelate with intracellular metal ions
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- Tajima Masamichi
- Div. Pharmacol., Dept. Diagn Ther Sci, Meikai Univ. Sch. Dent.
Bibliographic Information
- Other Title
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- ビスホスホネートは細胞内金属イオンとキレート形成することによって骨芽細胞のマイトファジーを誘導する
Abstract
<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>
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 93 (0), 3-P-377-, 2020
Japanese Pharmacological Society
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Keywords
Details 詳細情報について
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- CRID
- 1390283659860137728
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- NII Article ID
- 130007811942
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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