Role of non-apoptotic caspase in environmental electrophile-induced disorder of central nervous system
Project/Area Number |
19H04279
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 63030:Chemical substance influence on environment-related
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Research Institution | Tokyo University of Science |
Principal Investigator |
Ichihara Gaku 東京理科大学, 薬学部薬学科, 教授 (90252238)
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Co-Investigator(Kenkyū-buntansha) |
宗 才 東京理科大学, 薬学部薬学科, 助教 (20817267)
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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 |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2020: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
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Keywords | カスパーゼ / 神経変性 / 炎症 / 酸化ストレス / 神経突起 / ミクログリア / 神経毒性 / 非アポトーシス / 中枢神経 / 毒性 / 親電子性物質 |
Outline of Research at the Start |
本研究は環境化学物質のハザード評価においてこれまで見逃されてきた中枢神経障害の同定を可能にするとともに、アポトーシスと強く結びつけられて議論されることが多かったカスパーゼ-の非アポトーシス機能の解明およびその制御機構を明らかにする。本研究の成果は、環境化学物質による中枢神経障害だけでなく、広汎な神経変性疾患における非アポトーシス誘導性カスパーゼ-の役割の解明に資する。
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Outline of Final Research Achievements |
The study demonstrated that exposure to acrylamide induced expression of initiator caspase 8, inflammatory caspase 1 and 4 and proinflammatory cytokines. These results suggest receptor-mediated extrinsic pathway of cell death, not intrinsic pathway, is operating in acrylamide-exposed neurons, and intercellular signals from microglia play important role in neurite retraction. The study also shows that caspase 6, which is an effector caspase, in neurons is involved in acrylamide-induced neurodegeneration. The study demonstrates neuronal caspases are involved in neurite retraction and neurodegeneration without induction of neuronal apoptosis.
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Academic Significance and Societal Importance of the Research Achievements |
本研究は環境化学物質のハザード評価においてこれまで見逃されてきた中枢神経障害の同定を可能にするとともに、アポトーシスと強く結びつけられて議論されることが多かったカスパーゼ-の非アポトーシス機能が環境化学物質による神経障害に関与すること、ミクログリアからニューロンへの細胞間シグナルが神経変性誘導に貢献していることを明らかにした。本研究は産業現場における自律的な化学物質のリスク管理が求められている状況に対し、未知の化学物質の中枢神経毒性を予見するための有効なツール構築の基礎を提供する。
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Report
(4 results)
Research Products
(103 results)
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[Journal Article] Occupational exposure limits for acetaldehyde, 2-bromopropane, glyphosate, manganese and inorganic manganese compounds, and zinc oxide nanoparticle, and the biological exposure indices for cadmium and cadmium compounds and ethylbenzene, and carcinogenicity, occupational sensitizer, and reproductive toxicant classifications2021
Author(s)
The Committee for Recommendation of Occupational Exposure Limits, Japan Society for Occupational Health
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Journal Title
Journal of Occupational Health
Volume: 63
Issue: 1
Pages: n/a
DOI
NAID
ISSN
1341-9145, 1348-9585
Related Report
Peer Reviewed / Open Access
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[Journal Article] Functionalized surface-charge SiO2 nanoparticles induce pro-inflammatory responses, but are not lethal to Caco-2 cells.2020
Author(s)
Tada-Oikawa S, Eguchi M, Yasuda MT, Izuoka K, Ikegami A, Vranic S, Boland S, Tran L, Ichihara G, Ichihara S
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Journal Title
Chem Res Toxicol
Volume: 印刷中
Issue: 5
Pages: 1226-1236
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Proteomic analysis of liver proteins of mice exposed to 1,2-dichloropropane.2020
Author(s)
Zhang X, Morikawa K, Mori Y, Zong C, Zhang L, Garner E, Huang C, Wu W, Chang J, Nagashima D, Sakurai T, Ichihara S, Oikawa S, Ichihara G.
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Journal Title
Arch Toxicol.
Volume: 94
Issue: 8
Pages: 2691-2705
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Occupational exposure limits for cumene, 2,4-dichlorophenoxy acetic acid, silicon carbide whisker, benzyl alcohol, and methylamine, and carcinogenicity, occupational sensitizer, and reproductive toxicant classifications2019
Author(s)
The Committee for Recommendation of Occupational Exposure Limits, Japan Society for Occupational Health
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Journal Title
Journal of Occupational Health
Volume: 61
Issue: 4
Pages: 328-330
DOI
NAID
ISSN
1341-9145, 1348-9585
Year and Date
2019-07-20
Related Report
Peer Reviewed / Open Access
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[Journal Article] Particle toxicology and health - where are we?2019
Author(s)
Riediker M, Zink D, Kreyling W, Oberdorster G, Elder A, Graham U, Lynch I, Duschl A, Ichihara G, Ichihara S, Kobayashi T, Hisanaga N, Umezawa M, Cheng TJ, Handy R, Gulumian M, Tinkle S, Cassee F
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Journal Title
Part Fibre Toxicol
Volume: 印刷中
Issue: 1
Pages: 19-19
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Correction to: Particle toxicology and health - where are we?2019
Author(s)
Riediker Michael、Zink Daniele、Kreyling Wolfgang、Oberd?rster G?nter、Elder Alison、Graham Uschi、Lynch Iseult、Duschl Albert、Ichihara Gaku、Ichihara Sahoko、Kobayashi Takahiro、Hisanaga Naomi、Umezawa Masakazu、Cheng Tsun-Jen、Handy Richard、Gulumian Mary、Tinkle Sally、Cassee Flemming
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Journal Title
Particle and Fibre Toxicology
Volume: 16
Issue: 1
Pages: 26-26
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Effect of Nrf2 deletion on inflammatory response in lung of female mice exposed to zinc oxide nanoparticles2021
Author(s)
Sehsah R, Wu W, Ichihara S, Hashimoto N, Hasegawa Y, Zong C, Yamazaki K, Sato H, Itoh K, Yamamoto M, Ali Elsayed A, El-Bestar S, Kamel E, Ichihara G
Organizer
NanoTox2021
Related Report
Int'l Joint Research
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[Presentation] Pulmonary effects of Fe3O4-PEG-PLGA nanoparticles in human bronchial epithelial cells and in wild type and Nrf2 knockout mice following pharyngeal aspiration2021
Author(s)
Sato H, Zong C, Devineau S, McCord C, Ichihara S, Brookes O, Ekuban F, Itoh K, Yamamoto M, Boland S, Baeza-Squiban A, Ichihara G
Organizer
NanoTox2021
Related Report
Int'l Joint Research
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[Presentation] Role of macrophages in cytotoxicity, reactive oxygen species production and DNA damage in 1,2-dichloropropane-exposed human cholangiocytes in vitro2021
Author(s)
Abigail EKUBAN, Cai ZONG, Frederick Adams EKUBAN, Yusuke KIMURA, Ryoya TAKIZAWA, Kota MORIKAWA, Kazuo KINOSHITA, Sahoko ICHIHARA, Seiichiroh OHSAKO, Gaku ICHIHARA
Organizer
第48回日本毒性学会学術年会
Related Report
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[Presentation] Pulmonary effects of Fe3O4-PEG-PLGA nanoparticles in wild type and Nrf2 knockout mice following pharyngeal aspiration2021
Author(s)
Harue SATO, Cai ZONG, Stephanie DEVINEAU, Claire MCCORD, Sahoko ICHIHARA, Oliver BROOKES, Frederick Adams EKUBAN, Ken ITOH, Masayuki YAMAMOTO, Sonja BOLAND, Armelle BAEZA-SQUIBAN, Gaku ICHIHARA
Organizer
第48回日本毒性学会学術年会
Related Report
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[Presentation] Fe3O4-PEG-PLGA ナノ粒子の経気道曝露が肺にもたらす影響とNrf2 の役割2021
Author(s)
佐藤春恵, 宗才, Stephanie Devineau, Claire McCord, 市原佐保子, Oliver Brookes, 伊東健, 山本雅之, Sonja Boland, Armelle Baeza-Squiban, 市原学
Organizer
フォーラム2021 衛生薬学・環境トキシコロジー
Related Report
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[Presentation] Pulmonary effects of Fe3O4-PEG-PLGA nanoparticles in human bronchial epothalial cells and in wild type and Nrf2 knockout mice following pharyngeal aspiration2021
Author(s)
H. Sato, C. Zong, S. Devineau, C. McCord, S. Ichihara, O. Brookes, K.Itoh, M. Yamamoto, S. Boland, A. Baeza-Squiban, G. Ichihara
Organizer
SOT2021(米国毒性学会)
Related Report
Int'l Joint Research
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