Role of autophagy dysfunction in environmental electrophile-induced cognitive disorder
Project/Area Number |
16H02965
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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 |
Research Field |
Risk sciences of radiation and chemicals
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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) |
梅澤 雅和 東京理科大学, 研究推進機構総合研究院, 研究員 (60615277)
櫻井 敏博 東京理科大学, 薬学部薬学科, 助教 (70568253)
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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 |
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
|
Keywords | 神経毒性 / オートファジー / 炎症 / ミクログリア / アクリルアミド / 細胞死 / 認知障害 / 神経炎症 / 親電子性物質 / 認知機能 |
Outline of Final Research Achievements |
The present study demonstrated that exposure to acrylamide, an electrophile, induced neuroinflammation and microglial activation as well as inducing expression of autophagy-related protein. The expression of autophagy-related protein was temporary, suggesting the difficulty in use of this protein as a biomarker to visualize the toxicity of acrylamide to the central nervous system. On the other hand, the study showed that the inflammation-related or microglia-specific proteins are promising for visualization of the toxicity to the central nervous system as they are expressed persistently.
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Academic Significance and Societal Importance of the Research Achievements |
フロン代替物質、食品中にも含まれるアクリルアミドなどの環境化学物質が引き起こす中枢神経障害、認知機能障害において炎症が果たす役割を明らかにするとともに、炎症を制御するオートファジー関連分子の動態を明らかにした。本研究は炎症関連タンパクが中枢神経毒性を予測するバイオマーカーとして見込みのあるタンパクであることを示した。本研究成果は、環境化学物質だけでなく医薬品の副作用の予測、環境要因による認知機能障害を予防するために有用である。
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Report
(4 results)
Research Products
(139 results)
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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
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Occupational Exposure Limits for ethylidene norbornene, ethyleneimine, benomyl, and 2,3-epoxypropyl methacrylate, and classifications on carcinogenicity2018
Author(s)
Committee for Recommendation of Occupational Exposure Limits, Japan Society for Occupational Health, Araki A, Azuma K, Endo G, Endo Y, Fukushima T, Hara K, Hori H, Horie S, Horiguchi H, Ichiba M, Ichihara G, Ikeda M, Ishitake T, Ito A, Ito Y, Iwasawa S, Kakumu T, Kamijima M, Karita K.
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Journal Title
Journal of Occupational Health
Volume: 60
Issue: 4
Pages: 333-335
DOI
NAID
ISSN
1341-9145, 1348-9585
Year and Date
2018-07-20
Related Report
Peer Reviewed / Open Access
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[Journal Article] The DNA methylation profile of liver tumors in C3H mice and identification of differentially methylated regions involved in the regulation of tumorigenic genes.2018
Author(s)
Matsushita J, Okamura K, Nakabayashi K, Suzuki T, Horibe Y, Kawai T, Sakurai T, Yamashita S, Higami Y, Ichihara G, Hata K, Nohara K
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Journal Title
BMC Cancer
Volume: 18
Issue: 1
Pages: 317-317
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Carcinogenicity of isobutyl nitrite, β-picoline, and some acrylates2018
Author(s)
Kromhout H, Friesen M, Marques MM, Sergi CM, Abdallah M, Benke G, Cesta M, Germolec D, Houck K, Ichihara G, Jameson CW, Kanno J, Pogribny I, Svendsen C, Benbrahim-Tallaa L, Guyton KZ, Grosse Y, El Ghissassi F, Bouvard V, Hall A.
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Journal Title
The Lancet Oncology
Volume: 19
Issue: 8
Pages: 1020-1022
DOI
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Peer Reviewed / Int'l Joint Research
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[Journal Article] Pulmonary Hypofunction due to Calcium Carbonate Nanomaterial Exposure in Occupational Workers: A Cross-sectional Study2018
Author(s)
Guoliang Li, Lihong Liang, Jingchao Yang, Lihai Zeng, Zhiwei Xie, Yizhou Zhong, Xiaolin Ruan, Ming Dong, Zhanhong Yang, Guanchao Lai, Weixin Huang, Aichu Yang, Jiabing Chen, Banghua Wu, Huaming Xu, Dezhi Meng, Shijie Hu, Lihua Xia, Xingfen Yang, Laiyu Li, Sahoko Ichihara, Gaku Ichihara, Hanlin Huang, Zhenlie Huang
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Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Exposure assessment and heart rate variability monitoring in workers handling titanium dioxide particles-a pilot study.2016
Author(s)
Ichihara S, Li W, Omura S, Fujitani Y, Liu Y, Wang Q, Hiraku Y, Hisanaga N, Wakai K, Ding X, Kobayashi T, Ichihara G.
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Journal Title
J. Nanopart. Res.
Volume: 18
Issue: 3
Pages: 52-52
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Preliminary characterization of a murine model for 1-bromopropane neurotoxicity: Role of cytochrome P4502016
Author(s)
C. Zong, C.E. Garner, C. Huang, X. Zhang, L. Zhang, J. Chang, S. Toyokuni, H. Ito, M. Kato, T. Sakurai, S. Ichihara, G. Ichihara
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Journal Title
Toxicological Letters
Volume: 258
Pages: 249-258
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Titanium dioxide particle type and concentration influence the inflammatory response in Caco-2 cells2016
Author(s)
Tada-Oikawa S, Ichihara G, Fukatsu H, Shimanuki Y, Tanaka N, Suzuki Y, Murakami M, Izuoka K, Chang J, Wu W, Yamada Y, Ichihara S
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Journal Title
International Journal of Molecular Sciences
Volume: 17
Issue: 4
Pages: 576-576
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Mechanistic study on 1,2-dichloropropane induced cholangiocarcinoma2019
Author(s)
Cai Zong, Yusuke Kimura, Kazuo Kinoshita, Shigetada Takasu, Xiao Zhang, Toshihiro Sakurai, Yoshitaka Sekido, Sahoko Ichihara, Ginji Endo, Gaku Ichihara
Organizer
第18回分子予防環境医学研究会大会
Related Report
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[Presentation] Proteomic Analysis of Liver Proteins of Mice Exposed to 1,2-dichloropropane2019
Author(s)
X. Zhang, K. Morikawa, Y. Mori, C. Zong, L. Zhang, E. Garner, C. Huang, W. Wu, J. Chang, D. Nagashima, T. Sakurai, S. Ichihara, S. Oikawa and G. Ichihara
Organizer
Society of Toxicology 58th Annual Meeting (SOT2018)
Related Report
Int'l Joint Research
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[Presentation] Exposure to 1,2-dichloropropane upregulates the expression of activation-induced cytidine deaminase (AID) in human cholangiocytes co-cultured with macrophages2018
Author(s)
Cai Zong, Yusuke Kimura, Kazuo Kinoshita, Shigetada Takasu, Xiao Zhang, Toshihiro Sakurai, Yoshitaka Sekido, Sahoko Ichihara, Ginji Endo, Gaku Ichihara
Organizer
「予防を科学する炎症細胞社会学」領域班会議/若手ワークショップ
Related Report
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[Presentation] シリカナノ粒子の表面修飾とアポトーシス誘導能に関する研究2018
Author(s)
竹内 咲恵, サンドラ ブラニッチ, 渡邊 英里, 長田 百合果, 平野 明穂, 櫻井 敏博, 佐藤 聡, 市原 佐保子, ウ ウェンティン, ラン トラン, ソニア ボーランド, 市原 学
Organizer
第45回日本毒性学会学術年会
Related Report
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[Presentation] Exposure to 1,2-dichloropropane upregulates the expression of activation-induced cytidine deaminase (AID) in human cholangiocytes co-cultured with macrophages2018
Author(s)
Cai Zong, Yusuke Kimura, Kazuo Kinoshita, Shigetada Takasu, Xiao Zhang, Toshihiro Sakurai, Yoshitaka Sekido, Sahoko Ichihara, Ginji Endo, Gaku Ichihara
Organizer
第13回ナノ・バイオメディカル学会
Related Report
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[Presentation] Proteomic Analysis Of Hippocampal Proteins Of Rats Exposed To Acrylamide2017
Author(s)
D. Nagashima, L. Zhang, Y. Kitamura, S. Ichihara, Y. Wakayama, K. Morita, H. Katano, M. Sakai, E. Watanabe, T. Sakurai, S. Oikawa and G. Ichihara
Organizer
Society of Toxicology 56th Annual Meeting (SOT2017)
Place of Presentation
ボルチモア、米国
Year and Date
2017-03-12
Related Report
Int'l Joint Research
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[Presentation] Surface modifications of silica nanoparticles affect their uptake by the cells and subsequent pulmonary toxicity2017
Author(s)
Sandra Vranic, Eri Watanabe, Yurika Osada, Sahoko Ichihara, Wenting Wu, Toshihiro Sakurai, Toshihiro Suzuki, Ryo Abe, Sonia Boland, Lang Tran, Gaku Ichihara
Organizer
8th International Symposium on Nanotechnology, Occupational and Environmental Health
Related Report
Int'l Joint Research
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[Presentation] Role of P450 in Hepatotoxicity and Proliferation in Bile Duct Induced by Exposure to 1,2-Dichloropropane in Mice2016
Author(s)
Xiao Zhang, Cai Zong, Lingyi Zhang, Edwin Garner, Chinyen Huang, Wenting Wu, Jie Chang, Toshihiro Sakurai, Sahoko Ichihara, Gaku Ichihara
Organizer
第44回産業中毒・生物学的モニタリング研究会(日本産業衛生学会)
Place of Presentation
東京理科大学 神楽坂キャンパス 森戸記念館
Year and Date
2016-08-04
Related Report
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[Presentation] 1,2-ジクロロプロパン暴露マウスの肝毒性と胆管細胞の増殖におけるP450の役割2016
Author(s)
張 驍, Cai ZONG, Lingyi ZHANG, Edwin GARNER, Chinyen HUANG, Wenting WU, Jie CHANG, 桜井 敏博, 市原 佐保子, 市原 学
Organizer
第43回日本毒性学会学術年会
Place of Presentation
愛知県産業労働センター、名古屋市
Year and Date
2016-06-29
Related Report
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[Presentation] マウスにおけるシリカナノ粒子の表面修飾と炎症誘導作用との関係2016
Author(s)
渡邊 英里, サンドラ ブラニッチ, 市原 佐保子, 呉 文亭, 鈴木 利宙, 長田 百合果, ソニア ボーランド, ラン トラン, 櫻井 敏博, 安部 良, 市原 学
Organizer
第43回日本毒性学会学術年会
Place of Presentation
愛知県産業労働センター、名古屋市
Year and Date
2016-06-29
Related Report
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[Presentation] Surface Modifications Of Silica Nanoparticles Affect Their Uptake By The Cells And Subsequent Pulmonary Toxicity2016
Author(s)
Gaku Ichihara, Sandra Vranic, Sahoko Ichihara, Wenting Wu, Eri Watanabe, Arisa Hayashida, Yurika Osada, Toshihiko Sakurai, Sonja Boland, Lang Tran
Organizer
8th International Nanotoxicology Congress (Nanotox 2016)
Place of Presentation
Boston, USA
Year and Date
2016-06-01
Related Report
Int'l Joint Research
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[Presentation] Biomarkers of neurotoxicity2016
Author(s)
Ichihara G, Huang Z, Zhang L, Kitoh J, Takeuchi Y
Organizer
2016 Spring International Convention of The Pharmaceutical Society of Korea
Place of Presentation
Kim Daejung Convention Center, Gwangju, Korea
Year and Date
2016-04-18
Related Report
Int'l Joint Research / Invited
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