Studies on GRK2 as a potential drug discovery target for the sepsis syndrome
| Project/Area Number |
26460336
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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 | University of Toyama |
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Principal Investigator |
Hattori Yuichi 富山大学, 大学院医学薬学研究部(医学), 教授 (50156361)
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| Co-Investigator(Kenkyū-buntansha) |
大橋 若奈 富山大学, 大学院医学薬学研究部(医学), 助教 (50381596)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | GRK2 / 敗血症 / 炎症性サイトカイン / 活性酸素 / 敗血症性脳症 / ミクログリア / iNOS / β-Arrestin2 |
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| Outline of Final Research Achievements |
While GRK2 was originally discovered for its role in the process of desensitization of agonist-activated GPCRs, emerging evidence suggests that GRK2 can participate in the regulation of diverse cellular responses by phosphorylating a large number of non-GPCR substrates and interacting with a plethora of proteins involved in signaling and trafficking. GRK2 inhibitor was found to mitigate acute lung injury in mice with CLP-induced sepsis. Furthermore, we found using cultured mouse microglia that GRK2 was upregulated by LPS challenge and the knockdown of GRK2 gene expression abrogated the LPS-induced increase in the production of ROS and NO. The pharmacological inhibition of GRK2 was shown to downregulate ROS generation and iNOS expression and to prevent the histopathologic changes in brains of mice with CLP-induced sepsis. Thus, GRK2 may serve as a potentially interesting therapeutic target for sepsis syndrome, including sepsis-associated encephalopathy.
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Report
(4 results)
Research Products
(9 results)
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[Journal Article] Anti-Inflammatory Profile of Levosimendan in Cecal Ligation-Induced Septic Mice and in Lipopolysaccharide-Stimulated Macrophages.2015
Author(s)
Qiang Wang, Hiroki Yokoo, Michinori Takashina, Kimimasa Sakata, Wakana Ohashi, Lobna A Abdelzaher, Takahiro Imaizumi, Takuya Sakamoto, Kohshi Hattori, Naoyuki Matsuda, Yuichi Hattori
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Journal Title
Critical Care Medicine
Volume: 43巻，11号
Issue: 11
Pages: e508-e520
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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