Sensitive measurement of oxidized phospholipids as markers of oxidative stress and diseases.

• Project/Area Number: 24590094
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Showa University
• Principal Investigator: ITABE Hiroyuki 昭和大学, 薬学部, 教授 (30203079)
• Co-Investigator(Kenkyū-buntansha): KATO Rina 昭和大学, 薬学部, 助教 (30392400) ; OBAMA Takashi 昭和大学, 薬学部, 助教 (60395647)
• Research Collaborator: NOGUCHI Emiko
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 酸化LDL / 動脈硬化症 / 糖尿病 / 歯周病 / ELISA / 酸化リン脂質 / 酸化ストレス / リポタンパク質 / リゾホスファチジルコリン / LC-MS/MS / PAF-AH / 歯肉溝滲出液

Outline of Final Research Achievements

Oxidized low-density lipoprotein (oxLDL) present in vivo, which is involved in atherogenesis, has not been well characterized. In this study, we introduced LC-MS/MS procedure to quantify various oxidized phosphatidylcholine (oxPC) and lysoPC species with high sensitivity. With this technique we elucidated molecular species of oxPC and lysoPC produced during LDL oxidation process. In addition, we successfully separated in vivo oxLDL from human plasma for the first time using an anion-exchange column and a monoclonal antibody against oxidized PC. The in vivo oxLDL was revealed to be a particle with anionic charges and modification with oxPC. oxLDL could potentially be a marker to evaluate oxidative stresses in systemic diseases and/or local tissues.

Research Products

• [Journal Article] Dietary-cholesterol atherogenesis drastically changed during the juvenile period in rabbits. (2015)
  • Author(s): Yuka Keyamura, Chifumi Nagano, Masayuki Kohashi, Manabu Niimi, Masanori Nozako, Takashi Koyama, Hiroyuki Itabe, Tomohiro Yoshikawa
  • Journal Title: Biol. Pharm. Bull. Volume: 38
  • Peer Reviewed / Open Access
• [Journal Article] Add-on effect of probucol in atherosclerotic, cholesterol-fed rabbits treated with atorvastatin. (2014)
  • Author(s): Yuka Keyamura; Chifumi Nagano; Masayuki Kohashi; Manabu Niimi; Masanori Nozako; Takashi Koyama; Reiko Yasufuku; Ayako Imaizumi; Hiroyuki Itabe; Tomohiro Yoshikawa
  • Journal Title: PLoS ONE Volume: 9 Issue: 5 Pages: e96929-e96929
  • DOI: 10.1371/journal.pone.0096929
  • Peer Reviewed / Open Access
• [Journal Article] Time course-changes in phosphatidylcholine profile during oxidative modification of low-density lipoprotein (2014)
  • Author(s): Sasabe N, Keyamura Y, Obama T, Inoue N, Igarashi Y, Aiuchi T, Kato R, Yamaguchi T, Kuwata H, Iwamoto S, Miyazaki A, Hara S, Yoshikawa T, Itabe H
  • Journal Title: Lipids Health Dis Volume: 13 Issue: 1 Pages: 48-48
  • DOI: 10.1186/1476-511x-13-48
  • Peer Reviewed / Open Access
• [Journal Article] The apolipoprotein B concentration in gingival crevicular fluid increases in patients with diabetes mellitus. (2014)
  • Author(s): Noguchi E, Kato R, Ohno K, Mitsui A, Obama T, Hirano T, Itabe H, Yamamoto M.
  • Journal Title: Clinical Biochemistry Volume: 47 Issue: 1-2 Pages: 67-71
  • DOI: 10.1016/j.clinbiochem.2013.09.016
  • Peer Reviewed
• [Journal Article] Crucial role of perilipin-3 (TIP47) in formation of lipid droplets and PGE2 production in HL-60-derived neutrophils. (2013)
  • Author(s): Nose F, Yamaguchi T, Kato R, Aiuchi T, Obama T, Hara S, Yamamoto M, Itabe H.
  • Journal Title: PLoS One. Volume: 8 Issue: 8 Pages: 71542-71542
  • DOI: 10.1371/journal.pone.0071542
  • Peer Reviewed
• [Journal Article] Positive association between plasma levels of oxidized low-density lipoprotein and myeloperoxidase after hemodialysis in patients with diabetic end-stage renal disease. (2013)
  • Author(s): Kitabayashi C, Naruko T, Sugioka K, Yunoki K, Nakagawa M, Inaba M, Ohsawa M, Konishi Y, Imanishi M, Inoue T, Itabe H, Yoshiyama M, Haze K, Becker AE, Ueda M.
  • Journal Title: Hemodialysis International Volume: 17 Issue: 4 Pages: 557-567
  • DOI: 10.1111/hdi.12049
  • Peer Reviewed
• [Journal Article] Chronic kidney disease is associated with neovascularization and intraplaque hemorrhage in coronary atherosclerosis in elders: results from the Hisayama Study. (2013)
  • Author(s): Nakano T, Ninomiya T, Sumiyoshi S, Onimaru M, Fujii H, Itabe H, Nakashima Y, Sueishi K, Tsuruya K, Oda Y, Kitazono T, Kiyohara Y.
  • Journal Title: Kidney Int Volume: 84 Issue: 2 Pages: 373-380
  • DOI: 10.1038/ki.2013.111
  • Peer Reviewed
• [Journal Article] Chronic kidney disease is associated with neovascularization and intraplaque hemorrhage in coronary atherosclerosis in autopsy samples from Japanese elders: the Hisayama Study. (2013)
  • Author(s): Nakano T, Ninomiya T, Sumiyoshi S, Onimaru M, Fujii H, Itabe H, Nakashima Y, Sueishi, K Tsuruya K, Oda Y, Kitazono T, Kiyohara Y.
  • Journal Title: Kidney Internatinal Volume: in press
  • Peer Reviewed
• [Journal Article] Positive association between plasma levels of oxidized low density lipoprotein and myeloperoxidase after hemodialysis in patients with diabetic end-stage renal disease. (2013)
  • Author(s): Kitabayashi C, Naruko T, Sugioka K, Yunoki K, Nakagawa M, Inaba M, Ohsawa M, Konishi Y, Imanishi M, Inoue T, Itabe H, Yoshiyama M, Kazuo Haze, Becker AE.
  • Journal Title: Hemodialysis International Volume: in press
  • Peer Reviewed
• [Journal Article] Oxidized low-density lipoprotein as a biomarker of <i>in vivo</i> oxidative stress: from atherosclerosis to periodontitis (2012)
  • Author(s): Itabe H
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 51 Issue: 1 Pages: 1-8
  • DOI: 10.3164/jcbn.11-00020R1
  • NAID: 130004879278
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed
• [Journal Article] Chronic exposure to low frequency noise at moderate levels causes impaired balance in mice. (2012)
  • Author(s): Tamura H et al.
  • Journal Title: PLoS One Volume: 7 Issue: 6 Pages: e39807-e39807
  • DOI: 10.1371/journal.pone.0039807
  • Peer Reviewed
• [Journal Article] Chronic photo-oxidative stress and subsequent MCP-1 activation as causative factors for age-related macular degeneration (2012)
  • Author(s): Suzuki M, Tsujikawa M, Itabe H, Du ZJ, Xie P, Matsumura N, Fu X, Zhang R, Sonoda KH, Egashira K, Hazen SL, Kamei M
  • Journal Title: J Cell Sci Volume: Feb Pages: 2407-2415
  • DOI: 10.1242/jcs.097683
  • Peer Reviewed
• [Journal Article] Antiatherogenic effect of guava leaf extracts inhibiting leukocyte-type 1 12-lipoxygenase activity (2012)
  • Author(s): Yuki Kawakami, et al
  • Journal Title: Food Chem. Volume: 131 Issue: 4 Pages: 1069-1075
  • DOI: 10.1016/j.foodchem.2011.10.011
  • Peer Reviewed
• [Presentation] ヒト血漿中から分離した酸化LDLのapoB変性とリン脂質分子種の解析 (2015)
  • Author(s): 笹部直子、小浜孝士、矢澤快、大坪茉莉子、羽田幸代、井上望、相内敏弘、木庭新治、加藤里奈、山口智広、板部洋之
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] 酸化LDL生成時におけるリン脂質プロファイルの経時変化とLp-PLA2の役割 (2015)
  • Author(s): 笹部直子、毛谷村由佳、○小浜孝士、井上望、増子幸志、五十嵐優、相内敏弘、加藤里奈、山口智広、桑田浩、原俊太郎、吉川智博、板部洋之
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] ヒト血漿中の酸化LDLの性状 ～質量分析計を用いた脂質プロファイルの検討～ (2014)
  • Author(s): 笹部直子、○板部洋之、井上望、和田暁、梅宮大貴、佐々木愛紗、相内敏弘、加藤里奈、小浜孝士、山口智広
  • Organizer: 第56回日本脂質生化学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-06-06 – 2014-06-07
• [Presentation] 生体内酸化ストレスのマーカーとしての酸化LDL (2012)
  • Author(s): 板部 洋之
  • Organizer: 第65回日本酸化ストレス学会
  • Place of Presentation: 徳島
  • Invited
• [Presentation] Separation and characterization of oxidized LDL from human plasma (2012)
  • Author(s): Itabe H, Obama T, Koba S, Aiuchi T, Kato R, Yamaguchi T
  • Organizer: International Conferernce on Biochemistry of Lipids
  • Place of Presentation: Banff, Canada
• [Presentation] 新たな生活習慣病・歯周病とリポタンパク質
  • Author(s): 板部 洋之
  • Organizer: 第5回コレステロールダイナミクス研究会
  • Place of Presentation: 東京
  • Invited
• [Remarks] 生物化学部門のホームページ
  • URL: http://www10.showa-u.ac.jp/~biolchem/
• [Remarks] 生物化学部門のホームページ
  • URL: http://www10.showa-u.ac.jp/~biolchem/