Elucidation of a novel causative factor and investigation of effective foods in atherosclerosis

• Project/Area Number: 20700593
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Eating habits, studies on eating habits
• Research Institution: Nara Women's University
• Principal Investigator: ICHI Ikuyo Nara Women's University, 大学院・薬学系研究科, 助教 (50403316)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 動脈硬化 / 酸化ストレス / 脂質 / セラミド / 糖尿病 / LC-MS/MS / 抗酸化 / 脂質代謝

Research Abstract

Oxidative stress has been implicated in the development and progression of atherosclerosis. Ceramide has been implicated in regulating cell cycle arrest, apoptosis, and cellular senescence, and serves as an intracellular second messenger in these processes. Our previous study showed that ceramide concentrations in human plasma had a significantly positive correlation with lipid markers that associated with atherosclerosis. In this study, due to reveal the association of oxidative stress and ceramide metabolism in animal, we examined that oxidative stress via CCl_4 administration induces the changes of ceramide metabolism in not only the liver but also other organs such as the kidney. Tissue ceramide levels were analyzed using electrospray tandem mass spectrometry (LC-MS/MS). Next, we investigated whether ceramide metabolism was altered in damaged tissues by STZ administration, and whether ceramide accumulation is correlated with the pathogenesis of diabetes-induced complications. Although no differences in hepatic ceramide levels were observed between the control and diabetic rats, plasma and renal ceramide levels were significantly increased by STZ administration. The activations of sphingomyelinases, which hydrolyze sphingomyelin into ceramide, induced the increase of ceramide during STZ administration in plasma. Thus, Our data support the view that the excess accumulation of ceramide via oxidative stress may play an important role in the pathogenesis related atherosclerosis.

Research Products

• [Journal Article] Increase in plasma ceramide levels via secretory sphingomyelinase activity in streptozotocin-induced diabetic rats. (2011)
  • Author(s): K.Kobayashi, I.Ichi, T.Nakagawa, C.Kamikawa, Y.Kitamura, E.Koga, Y.Washino, Y.Hoshinaga, S.Kojo
  • Journal Title: Med.Chem.Comm. in press.
  • NAID: 120005494834
• [Journal Article] Increase in plasma ceramide levels via secretory sphingomyelinase activity in streptozotocin-induced diabetic rats (2011)
  • Author(s): K.Kobayashi, I.Ichi, T.Nakagawa, C.Kamikawa, Y.Kitamura, E.Koga, Y.Washino, Y.Hoshinaga, S.Kojo
  • Journal Title: Medicinal Chemistry Communications Volume: (in press)(掲載確定)
  • NAID: 120005494834
  • Peer Reviewed
• [Journal Article] Effect of nobiletin on lipid metabolism in rats (2011)
  • Author(s): E.Nagata, I.Ichi, R.Kataoka, M.Matsushima, N.Adachi, Y.Kitamura, T.Sasaki, S.Kojo
  • Journal Title: Journal of Health Science Volume: (In press)(掲載確定)
  • NAID: 120005494835
  • Peer Reviewed
• [Journal Article] Oxidative stress in the ischemic and non-ischemic parts of the rat liver after two-thirds ischemia/reperfusion. (2010)
  • Author(s): Y.Kitamura, Y.Washino, E.Koga, A.Ito, M.Kawagoe, C.Nakazaki, K.Kiso, I.Ichi, T.Matsura, S.Kojo.
  • Journal Title: Biosci Biotechnol Biochem. 74 Pages: 979-983
  • NAID: 10027554952
• [Journal Article] Effect of nobiletin on lipid metabolism in rats. (2010)
  • Author(s): E.Nagata, I.Ichi, R.Kataoka, M.Matsushima, N.Adachi, Y.Kitamura, T.Sasaki, S.Kojo
  • Journal Title: J.Health Sci. in press
  • NAID: 120005494835
• [Journal Article] S1P3-mediated cardiac fibrosis in sphingosine kinase 1 transgenic mice involves reactive oxygen species. (2010)
  • Author(s): N.Takuwa, S.Ohkura, S.Takashima, F.Wang, T.Tanaka, K.Hirano, Y.Banno, M.Sasaki, I.Ichi, Y.Okamoto, K.Yoshioka, W.Du, M.Okamura, N.Sugimoto, K.Mizugishi, Y.Nakamura, I.Ishii, M.Takamura, S.Kaneko, S.Kojo, K.Satouchi, K.Mitumori, J.Chun, Y.Takuwa
  • Journal Title: Cardiovasc.Res. 85 Pages: 484-493
  • NAID: 120001939472
• [Journal Article] Oxidative stress in the ischemic and non-ischemic parts of the rat liver after two-thirds ischemia/reperfusion. (2010)
  • Author(s): Y.Kitamura, Y.Washino, E.Koga, A.Ito, M.Kawagoe, C.Nakazaki, K.Kiso, I.Ichi, T.Matsura, S.Kojo
  • Journal Title: Biosci.Biotechnol.Biochem. 74 Pages: 979-983
  • NAID: 10027554952
• [Journal Article] Effect of celecoxib, a selective cyclooxygenase-2 inhibitor on carbon tetrachloride intoxication in rats. (2010)
  • Author(s): Y.Washino, E.Koga, Y.Kitamura, C.Kamikawa, K.Kobayashi, T.Nakagawa, C.Nakazaki, I.Ichi, S.Kojo
  • Journal Title: Biol.Pharm.Bull. 33 Pages: 707-709
  • NAID: 130000248023
• [Journal Article] Effect of celecoxib, a selective cyclooxygenase-2 inhibitor on carbon tetrachloride intoxication in rats (2010)
  • Author(s): Y.Washino, E.Koga, Y.Kitamura, C.Kamikawa, K.Kobayashi, T.Nakagawa, C.Nakazaki, I.Ichi, S.Kojo
  • Journal Title: Biological & Pharmaceutical Bulletin Volume: 33 Pages: 707-709
  • NAID: 130000248023
  • Peer Reviewed
• [Journal Article] Effect of celecoxib, a selective cyclooxygenase-2 inhibitor on carbon tetra chloride intoxication in rats (2010)
  • Author(s): Y Washino, E Koga, Y Kitamura, C Kamikawa, K Kobayashi, T Nakagawa, C Nakazaki, I Ichi, S Koji
  • Journal Title: Biological & Phamaceutical Bulletin 33 Pages: 707-709
  • NAID: 130000248023
  • Peer Reviewed
• [Journal Article] S1P3-mediated cardiac fibrosis in sphingosine kinase 1 transgenic mice involves reactive oxygen species (2010)
  • Author(s): N Takuwa, S Ohkura, S Takashima, K Ohtani, Y Okamoto, T Tanaka, K Hirano, S Usui, F Wang, W Du, K Yoshioka, Y Banno, M Sasaki, I Ichi, M Okamura, N Sugimoto, K Mizugishi, Y Nakanuma, I Ishii, M Takamura, S Kaneko, S Kojo, K Satouchi, K Mitumori, J Chun, Y Takuwa
  • Journal Title: Cardiovascular Reserch 85 Pages: 484-493
  • NAID: 120001939472
  • Peer Reviewed
• [Journal Article] Neutral sphingomyelinase-induced ceramide accumulation by oxidative stress during carbon tetrachloride intoxication. (2009)
  • Author(s): I.Ichi, C.Kamikawa, T.Nakagawa, K.Kobayashi, R.Kataoka, E.Nagata, Y.Kitamura, C.Nakazaki, T.Matsura, S.Kojo
  • Journal Title: Toxicology 261 Pages: 33-40
  • NAID: 110007482853
• [Journal Article] The beneficial effect of propolis on fat accumulation and lipid metabolism in rats fed a high-fat diet. (2009)
  • Author(s): I.Ichi, H.Hori, Y.Takashima, N.Adachi, R.Kataoka, K.Okihara, K.Hashimoto, S.Kojo
  • Journal Title: J.Food.Sci. 74
  • NAID: 110007575063
• [Journal Article] Effect of α-tocopherol on carbon tetrachloride intoxication in the rat liver. (2009)
  • Author(s): C.Iida, K.Fujii, E.Koga, Y.Washino, Y.Kitamura, I.Ichi, K.Abe, T.Matsura, S.Kojo
  • Journal Title: Arch.Toxicol. 83 Pages: 477-483
  • NAID: 110007340272
• [Journal Article] Neutral sphingomyelinase-unduced ceramide accumulation by oxidative stressduring carbon tetrachloride intoxication (2009)
  • Author(s): I Ichi, C Kamikawa, T Nakagawa, K Kobayashi, R Kataoka, E Nagata, Y Kitamura, C Nakazaki, T Matsura, S Kojo
  • Journal Title: Toxicology 261 Pages: 33-40
  • Peer Reviewed
• [Journal Article] Neutral sphingomyelinase-induced ceramide accumulation by oxidatives tress during carbon tetrachloride intoxication (2009)
  • Author(s): I Ichi, C Kamikawa, T Nakagawa, K Kobayashi, R Kataoka, E Nagata, Y Kitamura, C Nakazaki, T Matsura, S Kojo
  • Journal Title: Toxicology (In press)
  • Peer Reviewed
• [Journal Article] The beneficial effect of propolis on fat accumulation and lipid metabolism in rats fed a high-fat diet (2009)
  • Author(s): I. Ichi, H. Hori, Y. Takashima, N. Adachi, R. Kataoka, K Okihara, K. Hashimoto, S. Kojo
  • Journal Title: Journal of food science (In press)
  • NAID: 110007575063
  • Peer Reviewed
• [Journal Article] Effect of α-tocopherol on carbon tetrachloride intoxication in the rat liver (2009)
  • Author(s): C. Iida, K. Fujii, E. Koga, Y. Washino, Y. Kitamura, I. Ichi, K. Abe, T. Matsura, and S. Kojo
  • Journal Title: Archives of Toxicology 87 Pages: 477-483
  • NAID: 110007340272
  • Peer Reviewed
• [Journal Article] 地球におけるホモキラリティー生成機構 (2008)
  • Author(s): 市育代、小城勝相
  • Journal Title: 生化学 80 Pages: 331-336
  • NAID: 10021191673
• [Presentation] 四塩化炭素中毒時の酸化ストレスを介したセラミド代謝の変化 (2010)
  • Author(s): 市育代、上川千明、中川朋香、片岡亮子、永田絵里、北村佑子、中崎千尋、小林慧子、小城勝相
  • Organizer: 日本栄養・食糧学会第64回大会
• [Presentation] 糖尿病におけるセラミド代謝の変化 (2010)
  • Author(s): 小林慧子, 市育代, 上川千明, 中川朋香, 古賀枝里子, 鷲野由紀子, 北村佑子, 中崎千尋, 星長夕貴子, 小城勝相
  • Organizer: 第83回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] ラット肝臓の虚血・再灌流後の酸化ストレスの評価 (2010)
  • Author(s): 北村佑子、鷲野由紀子、古賀枝里子、伊藤綾香、中崎千尋、木曽かおり、市育代、松浦達也、小城勝相
  • Organizer: 第43回酸化反応討論会
  • Place of Presentation: 東京
• [Presentation] 肝臓の虚血・再灌流における酸化ストレス (2010)
  • Author(s): 小城勝相、北村佑子、鷲野由紀子、古賀枝里子、中崎千尋、木曽かおり、松浦達也、市育代
  • Organizer: 第63回日本酸化ストレス学会学術総会
  • Place of Presentation: 横浜
• [Presentation] プロポリスの脂質代謝改善作用機構 (2010)
  • Author(s): 市育代, 堀晴香, 高島夕佳, 足達乃理子, 片岡亮子, 橋本健二, 小城勝相
  • Organizer: 日本ビタミン学会第62回大会
  • Place of Presentation: 盛岡
• [Presentation] ビタミンEによる四塩化炭素中毒時の肝細胞死の抑制 (2009)
  • Author(s): 古賀枝里子、飯田ちなっ、藤井こずえ、鷲野由紀子、北村佑子、市育代、阿部皓一、小城勝相
  • Organizer: 第20回ビタミンE研究会
  • Place of Presentation: 奈良
  • Year and Date: 2009-01-25
• [Presentation] Carbon tetrachloride-induced oxidative stress and change of ceramide metabolism. (2009)
  • Author(s): I.Ichi, C.Kamikawa, T.Nakagawa, R.Kataoka, E.Nagata, K.Kobayashi, S.Kojo
  • Organizer: 4^<th> International Conference on Phospholipase A_2 and Lipid Mediators (PLM)
  • Place of Presentation: Tokyo
• [Presentation] Carbon tetrachloride-induced oxidative stress and change of ceramide metabolism (2009)
  • Author(s): 市育代, 上川千明, 中川朋香, 片岡亮子, 永田絵理, 小林慧子, 小城勝相
  • Organizer: he 1st International Conference on Lipid Hydroperoxide Biology and Medicine Sendai 2009
  • Place of Presentation: 仙台
• [Presentation] プロポリスによる体脂肪減少及び血清脂質改善作用のメカニズム (2009)
  • Author(s): 市育代、堀晴香、高島夕佳、足達乃理子、片岡亮子、沖原清司、橋本健二、小城勝相
  • Organizer: 第51回日本脂質生化学会
  • Place of Presentation: 名古屋
• [Presentation] 肝障害モデルラットにおける酸化ストレスを伴うセラミド動態の変化 (2009)
  • Author(s): 市育代、上川千明、中川朋香、小林慧子、片岡亮子、永田絵理、松浦達也、小城勝相
  • Organizer: 第62回日本酸化ストレス学会
  • Place of Presentation: 福岡
• [Presentation] 肝障害モデルラットにおける酸化ストレスを伴うセラミド動態の変化 (2009)
  • Author(s): 市育代、上川千明、中川朋香、小林慧子、片岡亮子、永田絵理、松浦達也、小城勝相
  • Organizer: 日本ビタミン学会第61回大会
  • Place of Presentation: 京都
• [Presentation] 四塩化炭素肝障害ラットにおけるビタミンEの肝細胞死抑制効果のメカニズム (2009)
  • Author(s): 市育代、古賀枝里子、飯田ちなつ、藤井こずえ、鷲野由紀子、北村佑子、阿部皓一、小城勝相
  • Organizer: 日本家政学会第61回大会
  • Place of Presentation: 大阪
• [Presentation] プロポリスによるラットの体脂肪および脂質減少効果 (2009)
  • Author(s): 市育代、堀晴香、高島夕佳、足達乃理子、片岡亮子、沖原清司、橋本健二、小城勝相
  • Organizer: 第63回日本栄養・食糧学会
  • Place of Presentation: 長崎
• [Presentation] 四塩化炭素中毒ラットのビタミンE抑制効果について (2009)
  • Author(s): 市育代、飯田ちなつ、藤井こずえ、古賀枝里子、鷲野由紀子、北村佑子、阿部皓一、松浦達哉、小城勝相
  • Organizer: 日本農芸化学会2009年度大会
  • Place of Presentation: 福岡
• [Presentation] 動脈硬化モデルマウスにおけるセラミドと危険因子との関係 (2008)
  • Author(s): 市育代, 小城勝相
  • Organizer: 第55回日本栄養改善学会学術総会
  • Place of Presentation: 鎌倉
  • Year and Date: 2008-09-06
• [Presentation] 動脈硬化の新規危険因子としてのセラミド (2008)
  • Author(s): 市育代
  • Organizer: 日本学術振興会産学協力研究会レドックス生命科学第170委員会
  • Place of Presentation: 静岡(招待講演)
  • Year and Date: 2008-07-31
• [Presentation] 四塩化炭素中毒におけるビタミンE経口投与がCに与える影響 (2008)
  • Author(s): 飯田ちなつ, 藤井こずえ, 古賀枝里子, 鷲野由紀子, 北村裕子, 市育代, 阿部皓一, 小城勝相
  • Organizer: ビタミンC研究委員会
  • Place of Presentation: 東京
  • Year and Date: 2008-07-05
• [Presentation] 四塩化炭素中毒ラットにおけるビタミンEの効果 (2008)
  • Author(s): 市育代、飯田ちなつ、藤井こずえ、古賀枝里子、鷲野由紀子、小城勝相
  • Organizer: 日本ビタミン学会第60回大会
  • Place of Presentation: 仙台
  • Year and Date: 2008-06-17
• [Presentation] 動脈硬化モデルマウスにおける血漿コレステロールとセラミドとの関係 (2008)
  • Author(s): 市育代、小城勝相
  • Organizer: 日本家政学会第60回大会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-31
• [Presentation] 動脈硬化の新規危険因子としてのセラミドレドックス生命科学 (2008)
  • Author(s): 市育代
  • Organizer: 第170委員会第19回研究会
• [Presentation] D-ガラクトサミンによる肝障害ラットにおけるジメチルスルホキシド(DMSO)の抗酸化作用と肝壊死阻害作用 (2008)
  • Author(s): 古賀枝里子、飯田ちなつ、藤井こずえ、鷲野由紀子、市育代、小城勝相
  • Organizer: 第62回栄養・食糧学会大会
  • Place of Presentation: 埼玉
• [Presentation] チオアセトアミド投与による肝炎モデルラットにおけるジメチススルポキシドの効果 (2008)
  • Author(s): 鷲野由紀子、岸岡輝実、飯田ちなつ、藤井こずえ、長江律子、大西優希、市育代、小城勝相
  • Organizer: 第62回栄養・食糧学会大会
  • Place of Presentation: 埼玉
• [Presentation] コレステロール及び高脂肪食がラットの体内セラミドに及ぼす影響 (2008)
  • Author(s): 上川千明、市育代、中原佳代子、木曽かおり、小城勝相
  • Organizer: 第62回栄養・食糧学会大会
  • Place of Presentation: 埼玉
• [Presentation] ガラクトサミン肝障害のDMSOによる効果 (2008)
  • Author(s): 市育代、飯田ちなつ、藤井こずえ、古賀枝里子、鷲野由紀子、小城勝相
  • Organizer: 第61回日本酸化ストレ冬学会学術集会
  • Place of Presentation: 京都
• [Presentation] 四塩化炭素肝炎のビタミンE経口投与による抑制 (2008)
  • Author(s): 市育代, 飯田ちなつ, 藤井こずえ, 古賀枝里子, 鷲野由紀子, 北村裕子, 阿部皓一, 小城勝相
  • Organizer: 第41回酸化反応討論会
  • Place of Presentation: 福岡
• [Presentation] チオアセトアミドによる肝障害モデルラットにおける酸化ストレスとMAPK活性化に対するDMSOの効果 (2008)
  • Author(s): 鷲野由紀子, 岸岡輝実, 飯田ちなつ, 藤井こずえ, 長江律子, 大西優希, 市育代, 小城勝相
  • Organizer: 2008年日本生化学会・日本分子生物学会合同年会
  • Place of Presentation: 神戸
• [Book] Antioxidants as biomarkers of oxidative stress.(Ed., G.Aldini, K.-J.Yeum, E.Niki, R.M.Russell)(In Biomarkers for Antioxidant Defense and Oxidative Damage : Principles and Practical Applications) (2010)
  • Author(s): I.Ichi, S.Kojo
  • Publisher: Wiley-Blackwell, Iowa, USA
• [Book] In Biomarkers for Antioxidant Defense and Oxidative Damage : Principles and Practical Applications (2010)
  • Author(s): I.Ichi, S.Kojo(Ed., G.Aldini, K.-J.Yeum, E.Niki, R.M.Russell)
  • Total Pages: 14
  • Publisher: Wiley-Blackwell
• [Book] In Biomarkers for Antioxidant Defense and Oxidative Damage : Principles and Practical Applications(Ed., G.Aldini, K.-J.Yeum, E.Niki and R.M.Russell), Antioxidants as biomarkers of oxidative stress (2010)
  • Author(s): I.Ichi, S.Kojo, et.al
  • Publisher: Wiley-Blackwell(In press)
• [Book] Biomarkers for Antioxidant Defense and Oxidative Damage : Principles and Practical Applications Antioxidants as biomarkers of oxidative stress (2009)
  • Publisher: Wiley-Blackwell, Iowa, USA(In press)
• [Remarks] ホームページ等