Pathogenesis and drug development using a mouse model of chronic obstructive pulmonary disease

• Project/Area Number: 21590974
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所) (2011); Toho University (2009-2010)
• Principal Investigator: ISHIGAMI Akihito 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究副部長 (50270658)
• Co-Investigator(Kenkyū-buntansha): HANDA Setsuko 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 助手 (30360697)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 閉塞性肺疾患 / 慢性閉塞性肺疾患 / ビタミンC / 老化 / COPD / 肺疾患

Research Abstract

We examined the effect of vitamin C depletion in lung from vitamin C depleted SMP30/GNL knockout mice by histopathologic and morphologic evaluations. Our results suggest that vitamin C protects lungs from oxidative stress and age-related lung diseases including cigarette smoke-induced chronic obstructive pulmonary disease(COPD).

Research Products

• [Journal Article] 17beta-Estradiol attenuates saturated fatty acid diet-induced liver injury in ovariectomized mice by up-regulating hepatic senescence marker protein-30 (2011)
  • Author(s): Fukui, M., Senmaru, T., Hasegawa, G., Yamazaki, M., Asano, M., Kagami, Y., Ishigami, A., Maruyama, N., Iwasa, K., Kitawaki, J., Itoh, Y., Okanoue, T., Ohta, M., Obayashi, H., Nakamura, N
  • Journal Title: Biochem Biophys Res Commun Volume: 415 Pages: 252-257
  • URL: http://dx.doi.org/10.1016/j.bbrc.2011.10.02
  • Peer Reviewed
• [Journal Article] Establishment and characterization of hepatocytes from an Immortomouse/SMP30/GNL knockout mouse hybrid lacking vitamin C to study vitamin C transport (2011)
  • Author(s): Amano, A., Handa, S., Aigaki, T., Shigemoto, K., Maruyama, N., Ishigami, A.
  • Journal Title: Journal of biochemistry Volume: 150 Issue: 6 Pages: 671-678
  • DOI: 10.1093/jb/mvr109
  • Peer Reviewed
• [Journal Article] Time course of vitamin C distribution and absorption after oral administration in SMP30/GNL knockout mice (2011)
  • Author(s): Iwama, M., Shimokado, K., Maruyama, N., Ishigami, A
  • Journal Title: Nutrition Volume: 27 Issue: 4 Pages: 471-478
  • DOI: 10.1016/j.nut.2010.04.010
  • NAID: 110008762053
  • Peer Reviewed
• [Journal Article] Time course of vitamin C distribution and absorption after oral administration into SMP30/GNL knockout mice (2011)
  • Author(s): Iwama, et.al.
  • Journal Title: Nutrition Volume: 27 Pages: 471-478
  • Peer Reviewed
• [Journal Article] Establishment and characterization of hepatocytes from an Immortomouse/SMP30/GNL knockout mouse hybrid lacking vitamin C to study vitamin C transport (2011)
  • Author(s): Amano, et.al.
  • Journal Title: J.Biochem. Volume: 50 Pages: 671-678
  • Peer Reviewed
• [Journal Article] 17beta-Estradiol attenuates saturated fatty acid diet-induced liver injury in ovariectomized mice by up-regulating hepatic senescence marker protein-30 (2011)
  • Author(s): Fukui, et.al.
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 215 Pages: 252-257
  • Peer Reviewed
• [Journal Article] Vitamin C deficiency attenuates liver fibrosis by way of up-regulated peroxisome proliferator-activated receptor-gamma expression in senescence marker protein 30 knockout mice (2010)
  • Author(s): Park, J. K., Ki, M. R., Lee, H. R., Hong, I. H., Ji, A. R., Ishigami, A., Park, S. I., Kim, J. M., Chung, H. Y., Yoo, S. E., Jeong, K. S
  • Journal Title: Hepatology Volume: 51 Issue: 5 Pages: 1766-1777
  • DOI: 10.1002/hep.23499
  • Peer Reviewed
• [Journal Article] Complete lack of vitamin C intake generates pulmonary emphysema in senescence marker protein-30 knockout mice (2010)
  • Author(s): Koike, K., Kondo, Y., Sekiya, M., Sato, Y., Tobino, K., Iwakami, S. I., Goto, S., Takahashi, K., Maruyama, N., Seyama, K., Ishigami, A
  • Journal Title: Am. J. Physiol. Lung Cell Mol. Physiol Volume: 298 Issue: 6 Pages: 784-792
  • DOI: 10.1152/ajplung.00256.2009
  • Peer Reviewed
• [Journal Article] Pathophysiological significance of senescence marker protein-30 (2010)
  • Author(s): Maruyama, N., Ishigami, A., Kondo, Y
  • Journal Title: Geriatr. Gerontol. Int Volume: 10 Issue: s1 Pages: 88-98
  • DOI: 10.1111/j.1447-0594.2010.00586.x
  • NAID: 10027273261
  • Peer Reviewed
• [Journal Article] Vitamin C deficiency attenuates liver fibrosis via up-regulated PPAR-gamma expression in SMP30 knock-out mice (2010)
  • Author(s): Park, et al.
  • Journal Title: Hepatology Volume: 51 Pages: 1766-1777
  • Peer Reviewed
• [Journal Article] Complete lack of vitamin C intake generates pulmonary emphysema in senescence marker protein-30 knockout mice (2010)
  • Author(s): Koike, et al.
  • Journal Title: Am.J.Physiol.Lung Cell Mol.Physiol. Volume: 298
  • Peer Reviewed
• [Journal Article] Pathophysiological significance of senescence marker protein-30 (2010)
  • Author(s): Maruyama, et al.
  • Journal Title: Geriatr.Gerontol.Int. Volume: 10(Sup.1)
  • Peer Reviewed
• [Journal Article] Over-expression of Senescence Marker Protein-30 Decreases Reactive Oxygen Species in Human Hepatic Carcinoma Hep G2 cells (2009)
  • Author(s): Handa, S., Maruyama, N. and Ishigami, A
  • Journal Title: Biol. Pharm. Bull Volume: 32 Pages: 1645-1648
  • NAID: 130000116921
  • URL: http://dx.doi.org/10.1248/bpb.32.1645
  • Peer Reviewed
• [Journal Article] Senescence marker protein 30 is up-regulated in kainate-induced hippocampal damage through ERK-mediated astrocytosis (2009)
  • Author(s): Son, T. G., Park, H. R., Kim, S. J., Kim, K., Kim, MS., Ishigami, A., Handa, S., Maruyama, N. Chung, H. Y. and Lee, J
  • Journal Title: J. Neurosci. Res Volume: 87 Issue: 13 Pages: 2890-2897
  • DOI: 10.1002/jnr.22122
  • Peer Reviewed
• [Journal Article] 瀬山邦明老化肺性閉塞性肺疾患(COPD)モデルマウス (2009)
  • Author(s): 小池建吾、石神昭人
  • Journal Title: ファルマシア Volume: 45 Pages: 1082-1086
• [Journal Article] Senescence marker protein 30 is up-regulated in kainate-induced hippocampal damage through ERK-mediated astrocytosis (2009)
  • Author(s): Son, et. al.
  • Journal Title: J.Neurosci.Res. 87 Pages: 2890-2897
  • Peer Reviewed
• [Journal Article] Over-expression of Senescence Marker Protein-30 Decreases Reactive Oxygen Species in Human Hepatic Carcinoma Hep G2 cells (2009)
  • Author(s): Handa, et. al.
  • Journal Title: Biol.Pharm.Bull. 32 Pages: 1645-1648
  • NAID: 130000116921
  • Peer Reviewed
• [Journal Article] 老化肺・慢性閉塞性肺疾患(COPD)モデルマウス (2009)
  • Author(s): 小池建吾, 石神昭人, 瀬山邦明
  • Journal Title: ファルマシア 45 Pages: 1082-1086
  • Peer Reviewed
• [Presentation] ビタミンC不足と寿命との関係 (2011)
  • Author(s): 石神昭人
  • Organizer: 平成23年度「ビタミンの日」記念講演会,日本バイオファクター協会
  • Place of Presentation: 東京
  • Year and Date: 2011-12-10
• [Presentation] ビタミンC不足と寿命との関係 (2011)
  • Author(s): 石神昭人
  • Organizer: 日本バイオファクター協会
  • Place of Presentation: 東京
  • Year and Date: 2011-12-10
• [Presentation] ビタミンCと老化、老化関連疾患 (2011)
  • Author(s): 石神昭人
  • Organizer: 日本基礎老化学会
  • Place of Presentation: 千葉
  • Year and Date: 2011-10-08
• [Presentation] ビタミンCの体内動態とその抗酸化能力 (2011)
  • Author(s): 石神昭人
  • Organizer: 第65回日本栄養・食糧学会大会シンポジウム「微量栄養素と生体機能との相互作用」
  • Place of Presentation: 東京
  • Year and Date: 2011-05-14
• [Presentation] ビタミンCのインスリン分泌における役割:SMP30/GNLノックアウトマウスを用いての検討 (2011)
  • Author(s): 千丸貴史、長谷川剛二、石神昭人、近藤嘉高、尾林博、岡田博史、浅野麻衣、山崎真裕、福井道明、中村直登
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
• [Presentation] ビタミンC欠乏マウスにおける活性酸素種は増加する (2011)
  • Author(s): 近藤嘉高、加賀美弥生、半田節子、石神昭人、丸山直記
  • Organizer: 第65回日本栄養・食糧学会
  • Place of Presentation: 東京
• [Presentation] Smp30/Sod1ダブルノックアウトマウスにおける肝臓の組織学的解析 (2011)
  • Author(s): 岩間水輝、野田義博、清水孝彦、近藤嘉高、丸山直記、石神昭人
  • Organizer: 日本ビタミン学会第63回大会
  • Place of Presentation: 広島
• [Presentation] ビタミンC欠乏がカテコールアミン生合成系に及ぼす影響 (2011)
  • Author(s): 天野晶子、角田誠、相垣敏郎、丸山直記、石神昭人
  • Organizer: 日本ビタミン学会第63回大会
  • Place of Presentation: 広島
• [Presentation] ヒトSMP30のX線結晶構造解析 (2011)
  • Author(s): 相澤真悟、千田美紀、相垣敏郎、丸山直記、石神昭人、千田俊哉
  • Organizer: 第11回日本蛋白質科学会年会
  • Place of Presentation: 大阪
• [Presentation] 特別シンポジウム「これからの基礎老化研究を考える」 (2011)
  • Author(s): 石神昭人
  • Organizer: 第34回日本基礎老化学会大
  • Place of Presentation: 東京
• [Presentation] SMP30/GNLノックアウトマウスを用いての検討 (2011)
  • Author(s): 千丸貴史, 他
  • Organizer: 日本糖尿病学会
  • Place of Presentation: 札幌
• [Presentation] ビタミンC欠乏マウスにおける活性酸素種は増加する (2011)
  • Author(s): 近藤嘉高, 他
  • Organizer: 日本栄養・食糧学会
  • Place of Presentation: 東京
• [Presentation] Smp30/Sod1ダブルノックアウトマウスにおける肝臓の組織学的解析 (2011)
  • Author(s): 岩間水輝, 他
  • Organizer: 日本ビタミン学会
  • Place of Presentation: 広島
• [Presentation] ビタミンC欠乏がカテコールアミン生合成系に及ぼす影響 (2011)
  • Author(s): 天野晶子, 他
  • Organizer: 日本ビタミン学会
  • Place of Presentation: 広島
• [Presentation] ヒトSMP30のX線結晶構造解析 (2011)
  • Author(s): 相澤真悟, 他
  • Organizer: 日本蛋白質科学会
  • Place of Presentation: 大阪
• [Presentation] ビタミンCの体内動態とその抗酸化能力 (2011)
  • Author(s): 石神昭人
  • Organizer: 日本栄養・食糧学会
  • Place of Presentation: 東京
• [Presentation] 慢性閉塞性肺疾患(COPD)とビタミンC (2010)
  • Author(s): 石神昭人
  • Place of Presentation: 東京
  • Year and Date: 2010-09-09
• [Presentation] 慢性閉塞性肺疾患(COPD)とビタミンC (2010)
  • Author(s): 石神昭人
  • Organizer: 抗加齢医学フォーラム
  • Place of Presentation: 目黒雅叙園(東京都)
  • Year and Date: 2010-09-09
• [Presentation] SMP30/GNL遺伝子破壊マウスを用いたビタミンCと老化、疾患研究 (2009)
  • Author(s): 石神昭人
  • Organizer: 第56回日本実験動物学会総会シンポジウムモデルマウスを用いた老化への分子遺伝学的アプローチ
  • Place of Presentation: 大宮
  • Year and Date: 2009-05-16
• [Presentation] SMP30/GNL遺伝子破壊マウスを用いたビタミンCと老化、疾患研究 (2009)
  • Author(s): 石神昭人
  • Organizer: 第56回日本実験物学会総会
  • Place of Presentation: 大宮ソニックシティー(埼玉)
  • Year and Date: 2009-05-16
• [Book] ビタミンCの事典 (2011)
  • Author(s): 石神昭人
  • Publisher: 東京堂出版
• [Remarks]
  • URL: http://www.vit-c.jp/index.php
• [Remarks]
  • URL: http://www.aging-regulation.jp/kenkyu/aging-vc-02.html
• [Remarks]
  • URL: http://www.mnc.toho-u.ac.jp/v-lab/vitamin/index.html