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01 奈良県立医科大学 >
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0122 学位請求論文 >
01221 博士論文(医学) >
2024年度 >
このアイテムの引用には次の識別子を使用してください:
http://hdl.handle.net/10564/4440
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タイトル: | Mitochondrial Calcium Uniporter (MCU) is Involved in an Ischemic Postconditioning Effect Against Ischemic Reperfusion Brain Injury in Mice |
その他のタイトル: | ミトコンドリアカルシウムユニポーター(MCU)は、マウスの虚血再灌流脳損傷に対す る虚血ポストコンディショニング効果に関与している |
著者: | Sasaki, Hiromitsu Nakagawa, Ichiro Furuta, Takanori Yokoyama, Shohei Morisaki, Yudai Saito, Yasuhiko Nakase, Hiroyuki |
キーワード: | Ischemic postconditioning (PostC) Mitochondrial calcium uniporter (MCU) NMDA receptor (NMDAR) Mitochondrial permeability transition pore (mPTP) |
発行日: | 2024年4月3日水曜日 |
出版者: | Springer |
引用: | Cellular and molecular neurobiology. 2024 Apr, vol.44, No.1, article no.32 |
抄録: | The phenomenon of ischemic postconditioning (PostC) is known to be neuroprotective against ischemic reperfusion (I/R) injury. One of the key processes in PostC is the opening of the mitochondrial ATP-dependent potassium (mito-KATP) channel and depolarization of the mitochondrial membrane, triggering the release of calcium ions from mitochondria through lowconductance
opening of the mitochondrial permeability transition pore. Mitochondrial calcium uniporter (MCU) is known as a highly sensitive transporter for the uptake of Ca2+ present on the inner mitochondrial membrane. The MCU has attracted attention as a new target for treatment in diseases, such as neurodegenerative diseases, cancer, and ischemic stroke. We considered
that the MCU may be involved in PostC and trigger its mechanisms. This research used the whole-cell patch-clamp technique on hippocampal CA1 pyramidal cells from C57BL mice and measured changes in spontaneous excitatory postsynaptic currents (sEPSCs), intracellular Ca2+ concentration, mitochondrial membrane potential, and N-methyl-d-aspartate receptor (NMDAR) currents under inhibition of MCU by ruthenium red 265 (Ru265) in PostC. Inhibition of MCU increased the occurrence of sEPSCs (p = 0.014), NMDAR currents (p < 0.001), intracellular Ca2+
concentration (p < 0.001), and dead cells (p < 0.001) significantly after reperfusion, reflecting removal of the neuroprotective effects in PostC. Moreover, mitochondrial depolarization in PostC with Ru265 was weakened, compared to PostC (p = 0.004). These results suggest that MCU affects mitochondrial depolarization in PostC to suppress NMDAR over-activation and prevent elevation of intracellular Ca2+ concentrations against I/R injury. |
内容記述: | 権利情報:© 2024. The Author(s).Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation,
distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source,
provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not
permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
URI: | http://hdl.handle.net/10564/4440 |
ISSN: | 1573-6830 |
DOI: | https://doi.org/10.1007/s10571-024-01464-7 |
学位授与番号: | 24601甲第945号 |
学位授与年月日: | 2025-03-14 |
学位名: | 博士(医学) |
学位授与機関: | 奈良県立医科大学 |
出現コレクション: | 2024年度
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