| Project/Area Number |
16K19029
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General medical chemistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
MATSUZAKI Kyoko 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (90568932)
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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 |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ストレス顆粒 / 老化 / ストレス |
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| Outline of Final Research Achievements |
Cells form transient aggregates of proteins and mRNA, which is called stress granules in response to certain types of stress. Cells can survive under stressful conditions by forming this stress granules and stop protein synthesis. In this research, I searched for novel compounds that regulate stress granule formation by using small compound library and identified three kinds of compounds that suppress stress granule formation in HeLa cells. I also found that suppression of stress granule formation increased the sensitivity of HeLa cells against anti-cancer agents.
On the other hand, I found that senescent skin HaCaT cells lost their ability to form stress granules. What is more, I identified some compounds that promote stress granule formation in HaCaT cells. Thus I’m trying to find out the effect of these compounds on senescence.
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| Academic Significance and Societal Importance of the Research Achievements |
固形癌の内部では、腫瘍血管の還流不全により低酸素状態に晒される領域が存在する。そのような領域内のがん細胞はストレス顆粒を形成し抗がん剤に抵抗性を示すため、がん治療の大きな障壁となっている。本研究で同定された三種類の化合物は、低酸素環境下でのストレス顆粒の形成を抑制し、抗がん剤への感受性を高めたことから、がん治療への応用が期待される。
また、高齢化が進む日本において、細胞老化とアンチエイジングは重要な研究課題であるが、本研究では老化細胞におけるストレス顆粒形成能の低下が示唆された。したがって、ストレス顆粒がアンチエイジングの新しい標的となることが期待され、学術的にも社会的にも意義は大きい。
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