Role of mitochondrial Ca2+ transporter in vascular function and vascular diseases
| Project/Area Number |
16K08565
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Tokushima Bunri University (2017-2018)
Fukuoka University (2016) |
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Principal Investigator |
Kita Satomi 徳島文理大学, 薬学部, 教授 (10461500)
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| Co-Investigator(Kenkyū-buntansha) |
奥田 裕子 京都大学, 医学研究科, 特定助教 (30709663)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | ミトコンドリア / Ca輸送体 / イオン輸送体 / 血管病 / 薬理学 / 輸送体 |
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| Outline of Final Research Achievements |
Mitochondria, the crucial organelle in ATP production, can act as a Ca2+ sink. Ca2+ enters mitochondria mainly via MCU, a mitochondrial Ca2+ uniporter, and is extruded by mitochondrial Na+/Ca2+ exchanger (NCLX). We created NCLX knockout mice and organelle-specific Ca2+ sensor to study the role of NCLX in vascular function and vascular diseases. Phenylephrine-induced vasoconstriction were suppressed in NCLX knockout mice compared with wild-type and MCU knockout mice. In this study, we also found that mitochondrial Ca2+ efflux via NCLX contribute to pathophysiology in vascular diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
ミトコンドリアはATPを産生する重要なオルガネラであるとともに、アポトーシスの誘導、活性酸素種（ROS）の生成など、細胞の生死に関わる多彩な機能を担っている。ミトコンドリアの形態や機能の変化と細胞機能や病態への関与など多くの研究がなされているが、ミトコンドリアCa2+動態とその機能的役割についてはこれまで明らかになっていない。本研究により、ミトコンドリアから細胞質へのCa2+放出が平滑筋収縮に機能的に働くことが示された。また、NCLXを介したCa2+放出が血管病に関与することが分かり、血管病の治療標的として期待される。
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Report
(4 results)
Research Products
(14 results)
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[Journal Article] Reduced expression of Na+ /Ca2+ exchangers is associated with cognitive deficits seen in Alzheimer's disease model mice2018
Author(s)
Moriguchi S, Kita S, Fukaya M, Osanai M, Inagaki R, Sasaki Y, Izumi H, Horie K, Takeda J, Saito T, Sakagami H, Saido TC, Iwamoto T, Fukunaga K
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Journal Title
Neuropharmacology
Volume: 131
Pages: 291-303
DOI
Related Report
Peer Reviewed
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[Journal Article] Reduced CaM Kinase II and CaM Kinase IV Activities Underlie Cognitive Deficits in NCKX2 Heterozygous Mice.2018
Author(s)
Moriguchi S, Kita S, Yabuki Y, Inagaki R, Izumi H, Sasaki Y, Tagashira H, Horie K, Takeda J, Iwamoto T, Fukunaga K.
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Journal Title
Mol Neurobiol
Volume: 55(5)
Pages: 3889-3900
DOI
Related Report
Peer Reviewed
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[Journal Article] A subset of cerebrovascular pericytes originates from mature macrophages in the very early phase of vascular development in CNS.2017
Author(s)
S. Yamamoto, M. Muramatsu, E. Azuma, M. Ikutani, Y. Nagai, H. Sagara, B.N. Koo, S. Kita, E. O’Donnell, T. Osawa, H. Takahashi, K.I. Takano, M. Dohmoto, M. Sugimori, I. Usui, Y. Watanabe, N. Hatakeyama, T. Iwamoto, I. Komuro, K. Takatsu, K. Tobe, S. Niida, N. Matsuda, M. Shibuya, M. Sasahara
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Journal Title
Scientific Reports
Volume: 7：3855
Pages: 1-16
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Na<sup>+</sup>/Ca<sup>2+</sup> exchanger contributes to stool transport in mice with experimental diarrhea2017
Author(s)
Nishiyama K, Tanioka K, Azuma YT, Hayashi S, Fujimoto Y, Yoshida N, Kita S, Suzuki S, Nakajima H, Iwamoto T, Takeuchi T.
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Journal Title
J. Vet. Med. Sci.
Volume: 79
Issue: 2
Pages: 403-411
DOI
NAID
ISSN
0916-7250, 1347-7439
Related Report
Peer Reviewed / Open Access
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