Stress response and its control in mitochondrial DNA damaged cells
| Project/Area Number |
16K11513
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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 |
Pathobiological dentistry/Dental radiology
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| Research Institution | Kagoshima University |
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Principal Investigator |
TOMITA Kazuo 鹿児島大学, 医歯学域歯学系, 助教 (60347094)
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| Co-Investigator(Kenkyū-buntansha) |
馬嶋 秀行 鹿児島大学, 医歯学域歯学系, 教授 (60165701)
佐藤 友昭 鹿児島大学, 医歯学域歯学系, 教授 (10284887)
犬童 寛子 鹿児島大学, 医歯学域歯学系, 准教授 (00301391)
桑原 義和 東北医科薬科大学, 医学部, 准教授 (00392225)
末永 重明 鹿児島大学, 医歯学域附属病院, 講師 (00136889)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | ミトコンドリア / 酸化ストレス / 遺伝子発現変化 / 細胞膜状態 / 遺伝子発現 / 細胞・組織 / ストレス / 遺伝子発現制御 / 電子伝達系 |
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| Outline of Final Research Achievements |
We investigated the factor that regulate oxidative stress using ρ0 cells, which lack mitochondrial DNA (mtDNA). As a result, ρ0 cells show sensitivity against hydrogen peroxide.
ρ0 cells also show higher plasma membrane lipid peroxidation than that of its parental cells. Furthermore, this plasma membrane status is mainly due to the lipid oxidative enzyme activity such as ALOX, but not anti-oxidative enzyme activity. Our results show that the mitochondria is important for the sensitivity to oxidative stress. Moreover, the plasma membrane state was defined by the enhancement of intracellular oxidative enzymes rather than the decrease of intracellular antioxidant enzymes.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、酸化ストレスに感受性のミトコンドリアDNAを欠失したρ0細胞において、親株に比べて遺伝子発現だけではなく細胞と外界を隔てる細胞膜の状態が変化していることを明らかにした。このことは、細胞膜状態を制御することによりがん細胞をよりストレスに感受性な状態にできる可能性を示す結果であり、今後、細胞膜状態を変化させる薬剤を用いてより効果的ながん治療を行う際に重要な知見を提供すると考えられ、社会的意義は大きい。また、これまでは抗酸化能を高めるということに主眼が置かれがちであったが、細胞内酸化酵素(リポキシゲナーゼ等)の関与も示唆され、治療に対して抗酸化以外のアプローチも提示できた。
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Report
(4 results)
Research Products
(65 results)
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[Journal Article] Data on the aquaporin gene expression differences among ρ0, clinically relevant radioresistant, and the parental cells of human cervical cancer and human tongue squamous cell carcinoma.2018
Author(s)
Takashi Y, Tomita K, Kuwahara Y, Nabika H, Igarashi K, Nagasawa T, Kurimasa A, Fukumoto M, Nishitani Y, Sato T.
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Journal Title
Data Brief.
Volume: 15;20
Pages: 402-410
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clinical Phenotype and Segregation of Mitochondrial 3243A> G mutation in 2 pairs of monozygotic twins,2016
Author(s)
Maeda K, Kawai H, Sanada M, Terashima T, Ogawa N, Idehara R, Makiishi T, Yasuda H, Sato S, Hoshi K, Yahikozawa H, Nishi K, Itoh Y, Ogasawara K, Tomita K, Indo HP, Majima HJ
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Journal Title
JAMA Neurolog
Volume: 20
Issue: 8
Pages: 990-993
DOI
Related Report
Peer Reviewed
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[Journal Article] Changes in mitochondrial homeostasis and redox status in astronauts following long stays in space.2016
Author(s)
Indo HP, Majima HJ, Terada M, Suenaga S, Tomita K, Yamada S, Higashibata A, Ishioka N, Kanekura T, Nonaka I, Haukins CL, Davis MJ, St Clair DK, Mukai C.
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Journal Title
Scientific Reports
Volume: 6
Issue: 1
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Sensitivity for hydrogen peroxide in ρ0 cells and involvement of membrane status.2018
Author(s)
Yuko Takashi, Kazuo Tomita, Yoshikazu Kuwahara, Sayuri Yamanishi, Hideki Nabika, Koh-ichi Tanaka, Junichi Kitanaka, Nobue Kitanaka, Motohiko Takemura, Nobuyoshi Nishiyama, Shouichi Miyawaki, Yoshihiro Nishitani, Tomoaki Sato.
Organizer
WCP2018
Related Report
Int'l Joint Research
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[Presentation] Neonatal maternal separation delays the GABA excitatory-to-inhibitory functional switch by inhibiting KCC2 expression and induces developmental disorders-like behaviors in mice.2018
Author(s)
Minami Furukawa, Takao Tsukahara, Sayuri Yamanishi, Kazuo Tomita, Yuko Takashi, Koh-ich Tanaka, Junichi Kitanaka, Nobue Kitanaka, Motohiko Takemura, Nobuyoshi Nishiyama, Yoshihiro Nishitani, Shouichi Miyawaki, Tomoaki Sato
Organizer
WCP2018
Related Report
Int'l Joint Research
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[Presentation] Histamine H3 receptor inverse agonists alleviate methamphetamine-induced behavioral abnormalities in mice via histamine H1 receptors.2018
Author(s)
Nobue Kitanaka, Junichi Kitanaka, Yukie Amatsu, Rena Ozawa, Miho Sato, Kotaku Hashimoto, Erina Hisatomi, Eri Kitao, Mari Mimura, Miyu Nakamura, Kenta Tagami, Koh-ichi Tanaka, Kazuo Tomita, Takao Tsukahara, Tomoaki Sato, Nobuyoshi Nishiyama, F. Scott Hall, George R. Uhl, Motohiko Takemura.
Organizer
WCP2018
Related Report
Int'l Joint Research
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[Presentation] Memantine induces stereotyped behaviors in mice.2018
Author(s)
Junichi Kitanaka, Nobue Kitanaka, Yoshiro Kubota, Yumi Mimura,Yukiya Okada, Sayaka Ogura, Koh-ichi Tanaka, Kazuo Tomita, Takao Tsukahara, Tomoaki Sato, Nobuyoshi Nishiyama F. Scott Hall, George R. U., Motohiko Takemura.
Organizer
WCP2018
Related Report
Int'l Joint Research
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[Presentation] Analysis of oxidative stress response in clinically relevant radioresistant cells.2018
Author(s)
Kazuo Tomita , Yoshikazu Kuwahara, Yuko Takashi, Sayuri Yamanishi, Hideki Nabika , Koh-ich Tanaka , Junichi Kitanaka , Nobue Kitanaka, Motohiko Takemura, Nobuyoshi Nishiyama, Shouichi Miyawaki, Manabu Fukumoto, Yoshihiro Nishitani, Akihiro Kurimasa, Tomoaki Sato.
Organizer
WCP2018
Related Report
Int'l Joint Research
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