2020 Fiscal Year Final Research Report
Intracellular mechanism for membran repair mediated by ADP-ribosylation
| Project/Area Number |
18K06903
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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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| Review Section |
Basic Section 48030:Pharmacology-related
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| Research Institution | Doshisha Women's College of Liberal Arts |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 細胞膜修復 / ADP-リボシル化修飾 |
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| Outline of Final Research Achievements |
Plasma membrane breaks occurs during various pathological conditions, which is directly linked to cell death. Hence, the membrane repair mechanism plays an important role in maintaining homeostasis for the living body. ADP-ribosylation is a post-translational modification of proteins in which ADP-ribose units are sequentially transferred from NAD+ to acceptor proteins by poly(ADP-ribose) polymerase (PARP).
In this study, we found that PARP1, a founding member of PARP family, was activated in response to membrane breaks and catalyzed poly(ADP-ribosyl)ation.Suppression of PARP1 expression by shRNAs or pretreatment with PARP inhibitors inhibited membrane repairs as well as poly(ADP-ribosyl)ation in the damaged area. These results indicate that PARP1 contributes to membrane repair.
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| Free Research Field |
分子生物学
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| Academic Significance and Societal Importance of the Research Achievements |
今後、本研究をさらに進めることで臨床応用に発展させていきたいと考えている。現在、器質的ダメージや虚血再灌流障害など細胞膜損傷に伴う病態に対する直接的な治療法は無い。たとえば、虚血性心疾患の治療薬として心臓の負荷の軽減や心機能を改善する効果を狙った対症的治療薬が用いられているが、細胞膜損傷を伴う心筋細胞死に対する直接的な治療薬はない。したがって、本研究は、ADP-リボシル化修飾酵素の未解明の部分を明らかにするという学術的意義に加え、細胞膜損傷によって惹起される疾患、たとえば心不全による心筋細胞死などに対する臨床応用に向けた理論的基盤を提供できたと考えている。
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