| Project/Area Number |
20K14454
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 14030:Applied plasma science-related
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| Research Institution | Kyushu University |
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Principal Investigator |
Attri Pankaj 九州大学, プラズマナノ界面工学センター, 准教授 (40868361)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Discontinued (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Protein folding / MD Simulation / Biophysical studies / Computational study / Mdm2 / p53 / Biophysical techniques / SARS-CoV-2 / NADPH oxidase / Plasma treated liquid / MDM2-p53 complex / antioxidant enzymes / Catalase enzyme / Superoxide Dismutase |
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| Outline of Research at the Start |
The conventional cancer therapies lack selectivity, and resistance to the treatment while plasma-mediated apoptosis induction acts selectively on tumor cells. However, the latest plasma oncology studies reveal that selectivity is not observed for all cancer cell lines. This may be due to the elevated levels of antioxidant enzymes in some cancer cells. Therefore, in this project, we will study the effect of cold atmospheric plasma on the structure and activity of antioxidant enzymes. Later, we will use this information to improve the efficiency and selectivity of the plasma treatment.
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| Outline of Final Research Achievements |
Target 1: Structural modification of NADPH oxidase activator (Noxa 1) by oxidative stress: An experimental and computational study. In this work, we demonstrate the effect of plasma effect on the structural changes of Noxa1 SH3 protein, one of the regulatory subunits of NOX1. The structural deformation of Noxa1 SH3 protein was analyzed by various experimental methods and by MD simulations. Target 2: Possible impact of plasma oxidation on the structure of C-terminal Domain of SARS-CoV-2 spike protein: A computational study. We checked the plasma effect on the structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike protein and interaction SARS-CoV-2-CTD with human Angiotensin-Converting Enzyme 2 (hACE2). Target 3: In this study we investigated the structural changes in Mdm2, p53, and the Mdm2-p53 before and after possible plasma oxidation through molecular dynamic (MD) simulations.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の学術的意義はプラズマ照射へのがん細胞の応答機序解明にある。我々はプラズマ処理によるNADPHオキシダーゼ・アクチベーター・プロテインとリゾチームの構造変化はアミノ酸の酸化によると示した。続いてSARS-CoV-2-CTDタンパク質の構造がプラズマ処理により不安定化し、酸化の抑制が結合自由エネルギーの減少に寄与すること、さらにプラズマで酸化されたMdm2はp53を阻害しないことを計算から示した。つまりプラズマ処理したがん細胞内の活性酸素の増加はp53によるカタラーゼの不活性化が原因と考えられる。以上の成果は新薬やワクチン、診断薬、治療薬の開発に繋がり、人類の健康へ貢献可能と期待できる。
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