2007 Fiscal Year Final Research Report Summary
Functional proteomic analysis of oxidatively modified proteins associated with senescence acceleration and prevention of pathological aging
| Project/Area Number |
17390170
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Mie University |
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Principal Investigator |
OIKAWA Shinji Mie University, Graduate School of Medicine, Associate Professor (10277006)
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| Co-Investigator(Kenkyū-buntansha) |
MURATA Mariko Mie University, Graduate School of Medicine, Professor (10171141)
NOMURA Shinsuke Mie University, Graduate School of Medicine, Associate Professor (20198625)
FURUKAWA Ayako Institute for Developmental Ressarch, Aichi Human Service Center, Department of Pathology, Researcher (10455537)
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| Project Period (FY) |
2005 – 2007
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| Keywords | reactive oxygen species / proteomics / oxidatively modified proteins / senescence acceleration / prevention / pathological aging / brain / oxidative stress |
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| Research Abstract |
The reactive oxygen species(ROS), such as superoxide anion(O_2^-), hydrogen peroxide(H_2O_2) and free hydroxyl radicals(OH), participate in damage to cellular molecules including proteins. Recent studies suggest that abnormal protein oxidation may play an important role in acceleration of aging. In this study, we performed the identification and characterization of carbonyl-modified proteins, protein oxidation products, in hippocampal CAl region after transient cerebral ischemia-reperfusion using two-dimensional gel electrophoresis with immunochemical detection of protein carbonyls(2D Oxyblot). Ischemia-reperfusion induces the release of ROS, and organs are severely damaged by ischemia-reperfusion. Using 2D Oxyblot analysis, we demonstrated for the first time that carbonyl modification of Hsp70 in CA1 region was extensively increased prior to the neuronal cell death induced by ischemic-reperfusion insult. Hsp70 molecular chaperones are known to be induced by oxidative stress and have n
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europrotective function. Therefore, we considered that ischemia-reperfusion-induced oxidative damage to Hsp70 in CA1 region may lead to loss of the neuroprotective function, which contributes to neuronal cell death. In addition, we identified carbonyl modification proteins in liver and brain of SAMP8, which exhibits remarkable deficits in learning and memory, from peptide mass fingerprints using MALDI-TOF mass spectrometry in combination with LC-MS/MS analysis. Carbonyl modification of Cu,Zn-SOD in liver at 3 months and hippocampal cholinergic neurostimulating peptide precursor protein(HCNP-pp) in brain at 9 months were higher in SAMP8 compared with control SAMR1. We concluded that progressive accumulation of oxidative damage to Cu,Zn-SOD, may cause dysfunction of defense systems against oxidative stress in SAMP8 with a higher oxidative states, leading to acceleration of aging. Therefore, the generation of drugs sharing both antioxidant and carbonyl scavenger properties represents a new therapeutic challenge in the treatment of oxidative stress-associated diseases. Less
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Research Products
(87 results)
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[Journal Article] 9-Nitroanthracene derivative as a precursor of anthraquinone for photodynamic therapy2007
Author(s)
Fukuhara, K., Oikawa, S., Hakoda, N., Sakai, Y., Hiraku, Y., Shoda, T., Saito, S., Miyata, N., Kawanishi, S., Okuda, H
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Journal Title
Bioorg Med Chem 15
Pages: 3869-3873
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] iNOS-dependent DNA damage via NF-kappaB expression in hamsters infected with Opisthorchis viverrini and its suppression by the antihelminthic drug praziquantel2006
Author(s)
Pinlaor, S., Hiraku, Y., Yongvanit, P., Tada-Oikawa, S., Ma, N., Pinlaor, P., Sithithaworn, P., Sripa, B., Murata, M., Oikawa, S., Kawanishi, S
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Journal Title
Int J Cancer 119
Pages: 1067-1072
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Mechanism for manganese enhancement of dopamine-induced oxidative DNA damage and neuronal cell death2006
Author(s)
Oikawa, S., Hirosawa, I., Tada-Oikawa, S., Furukawa, A., Nishiura, K., Kawanishi, S
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Journal Title
Free Radic Biol Med 41
Pages: 1748-1756
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Pravastatin increases survival and suppresses an increase in myocardial matrix metalloproteinase activity in a rat model of heart failure2006
Author(s)
Ichihara, S., Noda, A., Nagata, K., Obata, K., Xu, J., Ichihara, G., Oikawa, S., Kawanishi, S., Yamada, Y., Yokota, M
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Journal Title
Cardiovasc Res 69
Pages: 726-735
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Procyanidin B2 has anti-and pro-oxidant effects on metal-mediated DNA damage2005
Author(s)
Sakano, K., Mizutani, M., Murata, M., Oikawa, S., Hiraku, Y., Kawanishi, S
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Journal Title
Free Radic Biol Med 39
Pages: 1041-1049
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Oxidative DNA damage in relation to neurotoxicity in the brain of mice exposed to arsenic at environmentally relevant levels2005
Author(s)
Piao, F., Ma, N., Hiraku, Y., Murata, M., Oikawa, S., Cheng, F., Zhong, L., Yamauchi, T., Kawanishi, S., Yokoyama, K
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Journal Title
J Occup Health 47
Pages: 445-449
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Accumulation of 8-nitroguanine in the liver of patients with chronic hepatitis C2005
Author(s)
Horiike, S., Kawanishi, S., Kaito, M., Ma, N., Tanaka, H., Fujita, N., Iwasa, M., Kobayashi, Y., Hiraku, Y., Oikawa, S., Murata, K., Wang, J., Semba, R., Watanabe, S., Adachi, Y
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Journal Title
J Hepatol 43
Pages: 403-410
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Chemopreventive action of xanthone derivatives on photosensitized DNA damage2005
Author(s)
Hirakawa, K., Yoshida, M., Nagatsu, A., Mizukami, H., Rana, V., Rawat, M.S., Oikawa. S., Kawanishi, S
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Journal Title
Photochem Photobiol 81
Pages: 314-319
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Guanine-specific DNA damage induced by gamma-irradiated histone2005
Author(s)
Furukawa, A., Hiraku, Y., Oikawa, S., Luxford, C., Davies, M J., Kawanishi, S
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Journal Title
Biochem J 388
Pages: 813-818
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Nitrative and oxidative DNA damage in oral lichen planus in relation to human oral carcinogenesis2005
Author(s)
Chaiyarit, P., Ma, N., Hiraku, Y., Pinlaor, S., Yongvanit, P., Jintakanon, D., Murata, M., Oikawa, S., Kawanishi, S
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Journal Title
Cancer Sci 96
Pages: 553-559
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Nitrative and oxidative DNA damage in intrahepatic cholangiocarcinoma patients in relation to tumor invasion
Author(s)
Pinlaor, S., Sripa, B., Ma, N., Hiraku, Y., Yongvanit, P., Wongkham, S., Pairojkul, C., Bhudhisawasdi, V., Oikawa, S., Murata, M., Semba, R., Kawanishi, S
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Journal Title
World J Gastroenterol 11
Pages: 4644-4649
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Formation of 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine by nitric oxide (NO) and superoxide (0_2)2007
Author(s)
Shiko, Takeuchi, Mariko, Murata, Shinji, Oikawa, Yusuke, Hiraku, Shosuke, Kawanishi
Organizer
1st Asian Conference on Environmental Mutagens & 36th Annual Meeting of The Japanese Environmental Mutagen Society
Place of Presentation
Kitakyushu, Japan
Year and Date
20071128-30
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Mechanism of iNOS-dependent DNA damage in hamsters infected with Opisthorchis viverrini : a model of inflammation-related carcinogenesis2006
Author(s)
Saeko, T., Oikawa, Somchai, Pinlaor, Puangrat, Yongvanit, Yusuke, Hiraku, Ning, Ma, Mariko, Murata, Shinji, Oikawa, Shosuke, Kawanishi
Organizer
20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
Place of Presentation
Kyoto
Year and Date
2006-06-22
Description
「研究成果報告書概要(欧文)」より
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