Expression, functions, and synthesis regulation of reactive sulfur species in vascular endothelial cells
| Project/Area Number |
19K07089
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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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| Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
Kaji Toshiyuki 東京理科大学, 薬学部薬学科, 教授 (90204388)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 血管内皮細胞 / 活性イオウ分子 / TGF-β / FGF-2 / バイオオルガノメタリクス / 細胞内シグナル経路 / 動脈硬化 / 活性イオウ分子産生酵素 / 重金属 / 鉛 / 小胞体ストレス / 有機-無機ハイブリッド分子 / 銅錯体 / 細胞増殖因子 |
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| Outline of Research at the Start |
血管病変防御に重要な役割を果たしている血管内皮細胞における低分子量型活性イオウ分子の機能とその発現調節を担う細胞内シグナル経路を解明する。そのために，培養血管内皮細胞を用い，亜鉛イオンの毒性軽減や生体防御タンパク質メタロチオネインの誘導への役割や，内皮細胞機能調節因子，有害重金属および有機-無機ハイブリッド分子による活性イオウ分子産生酵素群の発現制御とそれを担う細胞内シグナル経路を解析する。
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| Outline of Final Research Achievements |
Vascular endothelial cells are the only cell type in direct contact with blood, covering the lumen of blood vessels with a monolayer. The reactive sulfur species is a molecule with an excess of sulfur atoms added to the thiol group of L-cysteine, but its function and regulation of expression in vascular endothelial cells are still unknown. This study suggest that reactive sulfur species are produced in vascular endothelial cells in response to exogenous chemicals as well as cytokines/growth factors, and that endothelial cell functions are regulated by the reactive sulfur species. The reactive sulfur species-producing enzymes involved in this response varied depending on the stimuli, and the intracellular signaling pathways mediating the induction of these enzymes were also found to be diverse.
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| Academic Significance and Societal Importance of the Research Achievements |
血管内皮細胞の機能障害は動脈硬化病変，高血圧，血栓症などの血管病変の要因となる。本研究は，血管内皮細胞における活性イオウ分子の機能と合成調節が活性イオウ分子産生酵素の特定とその酵素の誘導を介在する細胞内シグナル経路のレベルで明らかにしたものであり，血管内皮細胞の機能調節の解明を確実に一歩進めたものであり，動脈硬化などの血管病変の予防と治療に新しい視点と展開をもたらす知見を提供するものである。
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Report
(4 results)
Research Products
(28 results)
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[Journal Article] Sodium trisulfide, a sulfane sulfur donor, stimulates bovine aortic endothelial cell proliferation in culture2021
Author(s)
Takahashi, M., Iwai, R., Takasawa, R., Nakano, T., Fujie, T., Hara, T., Hara, Y., Yamamoto, C.* and Kaji, T.*
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Journal Title
The Journal of Toxicological Sciences
Volume: 46
Issue: 7
Pages: 341-344
DOI
NAID
ISSN
0388-1350, 1880-3989
Related Report
Peer Reviewed / Open Access
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[Journal Article] Synthesis of reactive sulfur species in cultured vascular endothelial cells after exposure to TGF-β1: Induction of cystathionine γ-lyase and cystathionine β-synthase expression mediated by the ALK5-Smad2/3/4 and ALK5-Smad2/3-ATF4 pathways2021
Author(s)
37.Takahashi, M., Fujie, T., Nakano, T., Hara, T., Shinkai, Y., Takasawa, R., Hara, Y., Kumagai, Y., Yamamoto, C.* and Kaji, T.*
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Journal Title
International Journal of Molecular Sciences
Volume: 22
Issue: 21
Pages: 11762-11762
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Fibroblast Growth Factor-2 Upregulates Reactive Sulfur Species Production <i>via</i> ERK1/2 Signal-Mediated Cystathionine γ-Lyase Induction in Cultured Bovine Aortic Endothelial Cells2021
Author(s)
Takahashi, M., Kubota, T., Fujie, T., Shinkai, Y., Kumagai, Y., Nakano, T., Hara, T., Yamamoto, C.* and Kaji, T.*
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Journal Title
BPB Reports
Volume: 4
Issue: 6
Pages: 175-181
DOI
NAID
ISSN
2434-432X
Related Report
Peer Reviewed / Open Access
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[Journal Article] Transcriptional induction of cystathionine γ-lyase, a reactive sulfur-producing enzyme, by copper diethyldithiocarbamate in cultured vascular endothelial cells2020
Author(s)
Tomoya Fujie, Akane Takahashi, Musubu Takahashi, Takato Hara, Asuka Soyama, Kosho Makino, Hideyo Takahashi, Chika Yamamoto, Yoshito Kumagai, Hiroshi Naka and Toshiyuki Kaji
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Journal Title
International Journal of Molecular Sciences
Volume: 21
Issue: 17
Pages: 6053-6053
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Zn(II)2,9-dimethyl-1,10-phenanthroline stimulates cultured bovine aortic endothelial cell proliferation2020
Author(s)
Takehiro Nakamura, Eiko Yoshida, Takato Hara, Tomoya Fujie, Chika Yamamoto, Yasuyuki Fujiwara, Fumihiko Ogata, Naohito Kawasaki, Ryo Takita, Masanobu Uchiyama and Toshiyuki Kaji
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Journal Title
RSC Advances
Volume: 10
Issue: 69
Pages: 42327-42337
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Possible mechanisms underlying transcriptional induction of metallothionein isoforms by tris(pentafluorophenyl)stibane, tris(pentafluorophenyl)arsane, and tris(pentafluorophenyl)phosphane in cultured bovine aortic endothelial cells2019
Author(s)
Tomoya Fujie, Fukuta Takenaka, Eiko Yoshida, Shuji Yasuike, Yasuyuki Fujiwara, Yasuhiro Shinkai, Yoshito Kumagai, Chika Yamamoto, Toshiyuki Kaji
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Journal Title
The Journal of Toxicological Sciences
Volume: 44
Issue: 5
Pages: 327-333
DOI
NAID
ISSN
0388-1350, 1880-3989
Related Report
Peer Reviewed / Open Access
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