Analysis of mitochondrial DNA as a cause of cancer-derived myocardial damage
Project/Area Number |
20K11260
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 59010:Rehabilitation science-related
|
Research Institution | Nara Medical University |
Principal Investigator |
Ohmori Hitoshi 奈良県立医科大学, 医学部, 研究員 (80213875)
|
Co-Investigator(Kenkyū-buntansha) |
國安 弘基 奈良県立医科大学, 医学部, 教授 (00253055)
|
Project Period (FY) |
2020-04-01 – 2023-03-31
|
Project Status |
Completed (Fiscal Year 2022)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
|
Keywords | がん性心筋障害 / DAMP / ミトコンドリアDNA / Covid-19 / HMGB1 / がん性悪液質 / 中鎖脂肪酸 / ケトン体 / サイトカイン / ミトコンドリア / エネルギー代謝障害 / がん性心筋悪液質 / 心筋分化 / 酸化ストレス / がん / 悪液質 / 心筋障害 |
Outline of Research at the Start |
近年、がん患者の死因として心機能障害が重視されているが、申請者はその原因として癌に由来する変性産物であるDAMPが心筋障害をもたらすことを見出した。さらに、そのDAMPの中でもミトコンドリアDNAが心筋の炎症性サイトカイン産生を促進し無菌性炎症を惹起したが、ミトコンドリアDNAに炎症を惹起する特異的な配列が存在する可能性が示唆された。本研究では、このDAMPコンセンサスとも考えられる配列を解明し、がん性心筋障害の診断マーカーに、さらに、治療標的として応用可能にする基礎的知見を得ることを目的とする。本研究の結果は、がん性心筋障害の機序を解明し、予防・治療を可能にすると期待される。
|
Outline of Final Research Achievements |
Among the mitochondrial DNA, a fragment of Complex V showed growth inhibition in rat cardiomyoblasts. Furthermore, we found a fragment with homology to Covid-19 in the Complex V gene sequence. This fragment, in the form of double-stranded DNA, impaired cellular function by inducing HMGB1 expression, oxidative stress and decreased ATP production. Furthermore, this fragment was detected in the blood of a rat model of cancer cachexia. These findings suggest that this Covid-19 homologous mitochondrial DNA fragment plays an important role in myocardial damage in cancer cachexia.
|
Academic Significance and Societal Importance of the Research Achievements |
がん患者における心筋障害は、患者予後を増悪する重要な因子であったが、その発生機序は不明な点が多かった。本研究では、ミトコンドリアDNAの中でもコンプレックスVに存在するCovid-19と相同性を有する配列が、心筋障害に有用な役割を果たすことを見出した。この結果は、がん性悪液質のみならず、コロナ感染症やその他のDAMPに関連する心筋障害において、診断や治療の標的となる物質の同定の可能性を示唆するもので、その意義は大きい。
|
Report
(4 results)
Research Products
(37 results)
-
-
-
-
-
[Journal Article] Short telomere lesions with dysplastic metaplasia histology may represent precancerous lesions of Helicobacter pylori-positive gastric mucosa2023
Author(s)
Fujiwara-Tani R, Takagi T, Mori S, Kishi S, Nishiguchi Y, Sasaki T, Ikeda M, Nagai K, Bhawal UK, Ohmori H, Fujii K, Kuniyasu H
-
Journal Title
International Journal of Molecular Sciences
Volume: 24(4)
Issue: 4
Pages: 3182-3182
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
-
-
[Journal Article] BRAF Mutation Is Associated with Hyperplastic Polyp-Associated Gastric Cancer2021
Author(s)
Fujiwara-Tani Rina、Okamoto Ayaka、Katsuragawa Hiroyuki、Ohmori Hitoshi、Fujii Kiyomu、Mori Shiori、Kishi Shingo、Sasaki Takamitsu、Nakashima Chie、Kawahara Isao、Hojo Yudai、Nishiguchi Yukiko、Mori Takuya、Mizumoto Takeshi、Nagai Kenta、Luo Yi、Kuniyasu Hiroki
-
Journal Title
International Journal of Molecular Sciences
Volume: 22
Issue: 23
Pages: 12724-12724
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
[Journal Article] Malic enzyme 1 is associated with tumor budding in oral squamous cell carcinomas.2020
Author(s)
Nakashima C, Kirita T, Yamamoto K, Mori S, Luo Y, Sasaki T, Fujii K, Ohmori H, Kawahara I, Mori T, Goto K, Kishi S, Fujiwara-Tani R, Kuniyasu H
-
Journal Title
Int J Mol Sci
Volume: 21
Issue: 19
Pages: 7149-7149
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Clostridium perfringens enterotoxin induced claudin-4 to activate YAP in oral squamous cell carcinomas.2020
Author(s)
Nakashima C, Yamamoto K, Kishi S, Sasaki T, Ohmori H, Fujiwara-Tani R Mori S, Kawahara I, Nishiguchi Y, Mori T, Kondoh M, Luo Y, Kirita T, Kuniyasu H
-
Journal Title
Oncotarget
Volume: 11
Issue: 4
Pages: 309-321
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
[Presentation] Differential effects of three medium-chain fatty acids on myocardial damage in a mouse cachexia model2022
Author(s)
Nukaga S, Fujiwara-Tani R, Mori T, Kawahara I, Goto K, Nishida R, Kishi S, Mori S, Miyagawa Y, Fujii K, Ohmori H, Kuniyasu H
Organizer
81th Annual Meeting of Japanese Association for Cancer
Related Report
-
[Presentation] Differences in the effects of three types of medium-chain fatty acids on skeletal myoblasts2022
Author(s)
Nishida R, Mori S, Mori T, Nukaga S, Kawahara I, Miyagawa Y, Goto K, Ohmori H, Kishi S, Fujiwara-Tani R, Kuniyasu H
Organizer
81th Annual Meeting of Japanese Association for Cancer
Related Report
-
-
-
-
[Presentation] Effect of nutritional intervention with medium-chain fatty acids and glucose on cancer-derived myocardial atrophy.2021
Author(s)
Nukaga S, Mori T, Kawahara I, Miyagawa Y, Goto K, Fujiwara-Tani R, Kishi S, Mori S, Fujii K, Ohmori H, Kuniyasu H
Organizer
80th Annual Meeting of Japanese Association for Cancer
Related Report
-
-
[Presentation] Effects of antioxidant vitamins on cancerous sarcopenia model mice.2021
Author(s)
Kawahara I, Mori T, Nukaga S, Miyagawa Y, Goto K, Wakatsuki Y, Ohmori H, Fujii K, Mori S, Fujiwara-Tani R, Kishi S, Kuniyasu H
Organizer
80th Annual Meeting of Japanese Association for Cancer
Related Report
-
-
-
-
[Presentation] Effects of medium-chain fatty acids on cancer-derived myocardial atrophy2020
Author(s)
Nukaga S, Mori T, Luo Y, Kawahara I, Miyagawa Y, Goto K, Fujiwara-Tani R, Kishi S, Mori S, Ohmori H, Kuniyasu H
Organizer
79th Annual Meeting of Japanese Association for Cancer
Related Report
-
-
-