Role of ischemia-inducible activator of G-protein signaling in cellular response to pathophysiological stimuli
Project/Area Number |
24590280
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
General physiology
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Research Institution | Aichi Medical University |
Principal Investigator |
SATO Motohiko 愛知医科大学, 医学部, 教授 (40292122)
|
Co-Investigator(Kenkyū-buntansha) |
NISHIMURA Naoki 愛知医科大学, 医学部, 講師 (40278362)
SATO Maki 愛知医科大学, 医学部, 助教 (60351102)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | シグナル伝達 / G蛋白質 / 心筋保護 / 循環器病学 / 循環器・呼吸器 |
Outline of Final Research Achievements |
We previously identified an ischemia-inducible G-protein activator, activator of G-protein signaling 8 (AGS8), which interacts directly with Gβγ and regulated a critical cascade leading apoptosis of cardiomyocyte under hypoxia. We tried to protect cardiomyocytes from hypoxic injury by disrupting AGS8 mediated Gβγ-singling. We developed a peptide (AGS8-peptide) that blocked the association of Gβγ with AGS8 based on amino acid sequences of the Gβγ binding domain of AGS8. AGS8-peptide successfully blocked the interaction of Gβγ with AGS8 in vitro. To evaluate effect of AGS8-peptide in vivo, rat neonatal cardiomyocytes were exposed to hypoxia (6 h)/reoxygenation (18 h). AGS8-peptide was successfully transferred to cardiomyocytes, and blocked apoptosis of cardiomyocytes. These data indicated an importance of AGS8 mediated Gβγ-signaling in apoptosis of cardiomyocytes, and its potential as novel therapeutic target.
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Report
(4 results)
Research Products
(64 results)
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[Journal Article] A magnetic anti-cancer compound for magnet-guided delivery and magnetic resonance imaging.2015
Author(s)
Eguchi H, Umemura M, Kurotani R, Fukumura H, Sato I, Kim J-H, Hoshino Y, Lee J, Amemiya N, Sato M, Hirata K, Sigh DJ, Masuda T, Yamamoto M, Urano T, Yoshida K, Tanigaki K, Yamamoto M, Sato M, Inoue S, Aoki I and Ishikawa Y.
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Journal Title
Sci. Rep.
Volume: 5
Issue: 1
Pages: 9194-9194
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Coupling of beta1-adrenergic receptor to type 5 adenylyl cyclase and its physiological relevance in cardiac myocytes.2015
Author(s)
Tsunematsu T, Okumura S, Mototani Y, Ohnuki Y, Jin H, Cai W, SuitaK, Sato I, Umemura M, Yokoyama U, Sato M, Fujita T, and Ishikawa Y.
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Journal Title
Biochem. Biophys. Res. Commun.
Volume: 458
Issue: 3
Pages: 531-535
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Oscillation of cAMP and Ca(2+) in cardiac myocytes: a systems biology approach2015
Author(s)
Kamide T, Okumura S, Ghosh S, Shinoda Y, Mototani Y, Ohnuki Y, Jin H, Cai W, Suita K, Sato I, Umemura M, Fujita T, Yokoyama U, Sato M, Furutani K, Kitano H, Ishikawa Y
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Journal Title
The Journal of Physiological Sciences
Volume: 65(2)
Issue: 2
Pages: 195-200
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Decreased serum osmolality promotes ductus arteriosus constriction.2014
Author(s)
Aoki R, Yokoyama U, Ichikawa Y, Taguri M, Kumagaya S, Ishiwata R, Yanai C, Fujita S, Umemura M, Fujita T, Okumura S, Sato M, Minamisawa S, Asou T, Masuda M, Iwasaki S, Nishimaki S, Seki K, Yokota S, Ishikawa Y.
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Journal Title
Cardiovascular Research
Volume: 104(2)
Issue: 2
Pages: 326-36
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Epac1-dependent phospholamban phosphorylation mediates the cardiac response to stresses.2014
Author(s)
Okumura S, Fujita T, Cai W, Jin M, Namekata I, Mototani Y, Jin H, Ohnuki Y, Tsuneoka Y, Kurotani R, Suita K, Kawakami Y, Hamaguchi S, Abe T, Kiyonari H, Tsunematsu T, Bai Y, Suzuki S, Hidaka Y, Umemura M, Ichikawa Y, Yokoyama U, Sato M, Ishikawa F, Izumi-Nakaseko H, Adachi-Akahane S, Tanaka H, Ishikawa Y
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Journal Title
J Clin Invest.
Volume: 124
Issue: 6
Pages: 2785-2801
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Hyperthermia generated with ferucarbotran (Resovis®) in an alternating magnetic field enhances cisplatin-induced apoptosis of cultured human oral cancer cells.2014
Author(s)
Sato I, Umemura M, Mitsudo K, Kioi M, Nakashima H, Iwai T Fujita T, Yokoyama U, Okumura S, Feng X, Ito K, Miyajima A, Makino A, Iwai M, Eguchi H, I wai T, and Ishikawa Y.
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Journal Title
J. Physiol. Sci.
Volume: 64
Issue: 3
Pages: 177-183
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Protection of cardiomyocytes from the hypoxia-mediated injury by a peptide targeting the activator of G-protein signaling 8.2014
Author(s)
Sato M, Hiraoka M, Suzuki H, Sakima M, Mamun, AA, Yamane Y, Fujita T, Yokoyama U, Okumura S, and Ishikawa Y.
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Journal Title
PLoS ONE.
Volume: 9
Issue: 3
Pages: e91980-e91980
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Disruption of Epac1 decreases phosphorylation of phospholamban and protects the heart against tresses.2014
Author(s)
Okumura S, Fujita T, Cai W, Jin M, Namekata I, Mototani Y, Jin H-L, Ohnuki Y, Tsuneoka Y, Kurotani R, Suita K, Kawakami Y, Hamaguchi S, Abe T, Kiyonari H, Tsunematsu T, Bai Y, Suzuki S, Hidaka Y, Umemura M, Ichikawa Y, Yokoyama U, Sato M, Ishikawa F, Izumi-Nakaseko H, Adachi-Akahane S, Tanaka H, Ishikawa Y.
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Journal Title
Journal of Clinical Investigation
Volume: 印刷中
Related Report
Peer Reviewed
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[Presentation] G蛋白制御因子由来ペプチドによる細胞機能制御.2015
Author(s)
Mamun AA, 林寿来, 鈴木洋子, 佐喜眞未帆, 佐藤麻紀, 西村直記, 犬飼洋子, 岩瀬敏, 佐藤元彦
Organizer
第120回日本解剖学会全国学術集会・第92回日本生理学会大会合同大会
Place of Presentation
神戸国際会議場(神戸市中央区港島中町6-9-1)
Year and Date
2015-03-21
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[Presentation] G蛋白制御因子は血管新生に必要である.2015
Author(s)
林寿来, Mamun AA, 鈴木洋子, 佐喜眞未帆, 佐藤麻紀, 西村直記, 犬飼洋子, 岩瀬敏, 佐藤元彦.
Organizer
第120回日本解剖学会全国学術集会・第92回日本生理学会大会合同大会
Place of Presentation
神戸国際会議場(神戸市中央区港島中町6-9-1)
Year and Date
2015-03-21
Related Report
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[Presentation] G蛋白活性調節因子による血管内皮細胞制御機構.2015
Author(s)
林寿来, マムンアブドゥラ, 鈴木洋子, 佐喜眞未帆, 佐藤麻紀, 西村直記, 犬飼洋子, 岩瀬敏, 佐藤元彦
Organizer
第88回日本薬理学会年会
Place of Presentation
名古屋国際会議場(名古屋市熱田区熱田西町1番1号)
Year and Date
2015-03-10
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[Presentation] 血管新生におけるG蛋白活性調節因子の役割.2014
Author(s)
林寿来, Mamun Abudulla Al, 佐喜眞未帆, 鈴木洋子, 西村直記, 犬飼洋子, 岩瀬敏, 佐藤元彦.
Organizer
第61回中部日本生理学会
Place of Presentation
名古屋市立大学医学部付属病院大ホール(名古屋市瑞穂区瑞穂町川澄1)
Year and Date
2014-11-08
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[Presentation] シンポジウム: 心疾患とシグナル伝達‐再生医療と創薬への展開. The role of activator of G-protein signaling 8 (AGS8), a receptor-independent regulatory protein for heterotrimeric G-proteins, in the hypoxia-induced apoptosis of cardiomyocytes.2014
Author(s)
佐藤元彦, 林寿来, マムンAA, 鈴木洋子, 佐喜眞未帆, 岩瀬敏, 犬飼洋子, 西村直記, 佐藤麻紀.
Organizer
第87回日本生化学会大会
Place of Presentation
国立京都国際会館(京都市左京区岩倉大鷺町422番地)
Year and Date
2014-10-15
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[Presentation] シンポジウム“心筋組織の恒常性維持機構とその破綻(オーガナイザー:佐藤元彦, 黒瀬等)” 心筋虚血関連G蛋白活性調節因子(AGS8)由来ペプチドによる低酸素誘導心筋アポトーシスの制御.
Author(s)
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第91回日本生理学会大会
Place of Presentation
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第91回日本生理学会大会
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XXI World Congress of Neurology
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