Involvement of Oxidized Phospholipids in Aberrant Expression of Adipocytokines

• Project/Area Number: 20590105
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Kumamoto University
• Principal Investigator: KUNIYASU Akihiko Kumamoto University, 大学院・生命科学研究部, 准教授 (90241348)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 医薬分子機能学 / 脂質 / ストレス / 生理活性 / 薬学

Research Abstract

In obesity, oxidative stress is involved in aberrant production of adipocytokines. We found that oxidized LDL enhances the productions of plasminogen activator inhibitor-1 and resistin, and their molecular mechanism includes the production of reactive oxygen species followed by ERK signaling activation. Taken together, anti-oxidant reagents or ERK inhibitors may be useful for the prevention and treatment for metabolic syndromes.

Research Products

• [Journal Article] Oxidized LDL and lysophosphatidylcholine stimulate plasminogen activator inhibitor-1 expression through reactive oxygen species generation and ERK1/2 activation in 3T3-L1 adipocytes (2011)
  • Author(s): Kuniyasu A., Tokunaga T., Yamamoto Y., Inoue S., Obama K., Kawahara K., Nakayama H.
  • Journal Title: Biochim. Biophys. Acta 1811 Pages: 153-162
  • Peer Reviewed
• [Journal Article] Targeting neuropilin-1 in human leukemia and lymphoma. (2011)
  • Author(s): Karjalainen K., Jaalouk D.E., Bueso-Ramos C.E., Zurita A.J., Kuniyasu A., Lichtiger B., O' Brien S., Kantarjian H.M., Cortes J.E., Koivunen E., Arap W., Pasqualini R.
  • Journal Title: Blood 117 Pages: 920-927
  • Peer Reviewed
• [Journal Article] Targeting neuropilin-1 in human leukemia and lymphoma. (2011)
  • Author(s): Karjalainen K., Jaalouk DE., Bueso-Ramos CE., Zurita AJ., Kuniyasu A..Lichtiger B., O'Brien S., Kantarjian HM., Cortes JE., Koivunen E., Arap W., Pasqualini R.
  • Journal Title: Blood Volume: 117 Pages: 920-927
  • Peer Reviewed
• [Journal Article] Oxidized LDL and lysophosphatidylcholine stimulate plasminogen activator inhibitor-1 expression through reactive oxygen species generation and ERK1/2 activation in 3T3-L1 adipocytes. (2011)
  • Author(s): Kuniyasu A., Tokunaga T., Yamamoto Y., Inoue S., Obama K., Kawahara K., Nakayama H.
  • Journal Title: Biochim.Biophys.Acta Volume: 1811 Pages: 153-162
  • Peer Reviewed
• [Journal Article] Interconversion between pure chemotactic ligands and chemoattractant/secretagogue ligands of neutrophil C5a receptor by a single amino acid substitution. (2010)
  • Author(s): Jia, N., Semba, U., Nishiura, H., Kuniyasu, A., Nsiama, T.K., Nishino, N., Yamamoto, T.
  • Journal Title: J. Leukoc. Biol. 87 Pages: 965-975
  • Peer Reviewed
• [Journal Article] Three-dimensional structure of α1-β complex in skeletal muscle dihydropyridine receptor by single particle electron microscopy (2010)
  • Author(s): Murata K., Nishimura S., Kuniyasu A., Nakayama H.
  • Journal Title: J. Electron Microsc. 59 Pages: 215-226
  • Peer Reviewed
• [Journal Article] Contribution of BCR-ABL-independent activation of ERK1/2 to acquired imatinib resistance in K562 chronic myeloid leukemia cells (2010)
  • Author(s): Nambu T., Araki N., Nakagawa A., Kuniyasu A., Kawaguchi T., Hamada A., Saito H.
  • Journal Title: Cancer Sci. 101 Pages: 137-142
  • NAID: 10027199844
  • Peer Reviewed
• [Journal Article] オートファジー誘導に基づく白血病治療薬の開発 (2010)
  • Author(s): 國安明彦
  • Journal Title: 薬事日報「研究戦略・YAKU学-研究現場から臨床へ-」
• [Journal Article] Interconversion between pure chemotactic ligands and chemoattractant/secretagogue ligands of neutrophil C5a receptor by a single amino acid substitution. (2010)
  • Author(s): Jia, N., Semba, U., Nishiura, H., Kuniyasu.A., Nsiama, T.K., Nishino, N., Yamamoto, T.
  • Journal Title: J.Leukoc.Biol. Volume: 87 Pages: 965-975
  • Peer Reviewed
• [Journal Article] Contribution of BCR-ABL-independent Activation of ERK1/2 to Acquired Imatinib Resistance in K562 Chronic Myeloid Leukemia Cells (2010)
  • Author(s): Nambu T, Araki N, Nakagawa A, Kuniyasu A, Kawaguchi T, Hamada A, Saito H
  • Journal Title: Cancer Sci. 101 Pages: 137-142
  • NAID: 10027199844
  • Peer Reviewed
• [Journal Article] Oral administration of synthetic retinoid Am80 (Tamibarotene) decreases brain β-amyloid peptides in APP23 mice (2009)
  • Author(s): Kawahara K., Nishi K., Suenobu M., Ohtsuka H., Maeda A., Nagatomo K., Kuniyasu A., Staufenbiel M., Nakagomi M., Shudo K., Nakayama H.
  • Journal Title: Biol. Pharm. Bull. 32 Pages: 1307-1309
  • Peer Reviewed
• [Journal Article] Marked induction of inducible nitric oxide synthase and tumor necrosis factor-α in rat CD40^+ microglia by comparison to CD40 microglia (2009)
  • Author(s): Kawahara K., Yoshida A., Koga K., Yokoo S., Kuniyasu A., Gotoh, T., Sawada M., Nakayama H.
  • Journal Title: J. Neuroimmunol. 208 Pages: 70-79
  • Peer Reviewed
• [Journal Article] Linkage between phosphorylation of the origin recognition complex and its ATP-binding activity in Saccharomyces cerevisiae (2009)
  • Author(s): Makise M., Takehara M., Kuniyasu A., Matsui N., Nakayama H., Mizushima T.
  • Journal Title: J. Biol. Chem. 284 Pages: 3396-3407
  • Peer Reviewed
• [Journal Article] A synthetic approach to develop peptide inhibitors selective for brain-type sodium channels on the basis of pompilidotoxin structure (2009)
  • Author(s): Yokote S., Setoguchi R., Shimizu E., Mishima N., Kawahara K., Kuniyasu A., Shirasaki S., Takahama K., Konno K., Kawai N., Yamaoka K., Kinoshita E., Nakayama H.
  • Journal Title: Heterocycles 79 Pages: 925-933
  • NAID: 120005255069
  • Peer Reviewed
• [Journal Article] オートファジーを誘導するペプチド (2009)
  • Author(s): 國安明彦
  • Journal Title: ケミカルエンジニヤリング 54 Pages: 819-824
• [Journal Article] Three-dimensional structure of alpha 1-beta complex in skeletal muscle dihydropyridine receptor by single particle electron microscopy (2009)
  • Author(s): Murata K, Nishimura S., Kuniyasu, A, Nakayama H
  • Journal Title: J.Electron Microsc. Pages: 1-12
  • Peer Reviewed
• [Journal Article] Oral administration of synthetic retinoid Am80(Tamibarotene)decreases brain beta-amyloid peptides in APP23 mice (2009)
  • Author(s): Kawahara K, Nishi K, Suenobu M, Ohtsuka H, Maeda A, Nagatomo K, Kuniyasu A, Staufenbiel M, Nakagomi M, Shudo K, Nakayama H
  • Journal Title: Biol.Pharm.Bull. 32 Pages: 1307-1309
  • NAID: 130000117237
  • Peer Reviewed
• [Journal Article] Marked induction of inducible nitric oxide synthase and tumor necrosis factor-α in rat CD40+ microglia by comparison to CD40 microglia (2009)
  • Author(s): Kawahara K., et al.
  • Journal Title: J. Neuroimmunol. 208 Pages: 70-79
  • Peer Reviewed
• [Journal Article] A synthetic approach to develop peptide inhibitors selective for brain-type sodium channels on the basis of pompilidotoxin structure. (2009)
  • Author(s): Yokote S., et al.
  • Journal Title: Heterocycles 79 Pages: 925-933
  • Peer Reviewed
• [Journal Article] Linkage between phosphorylation of the origin recognition complex and its ATP-binding activity in Saccharomyces cerevisiae. (2009)
  • Author(s): Makise M., et al.
  • Journal Title: J. Biol. Chem. 284 Pages: 3396-3407
  • Peer Reviewed
• [Journal Article] Constitutive overexpression of P-glycoprotein, rather than breast cancer resistance protein or organic cation transporter 1, contributes to acquisition of imatinib羊esistance in K562 cells (2008)
  • Author(s): Hirayama C., Watanabe H., Nakashima R., Nanbu T., Hamada A., Kuniyasu A., Nakayama H., Kawaguchi T., Saito H.
  • Journal Title: Pharm. Res. 25 Pages: 827-835
  • Peer Reviewed
• [Journal Article] Combinatorial targeting of the macropinocytotic pathway in leukemia and lymphoma cells (2008)
  • Author(s): Nishimura S., Takahashi S., Kamikatahira H., Kuroki Y., Jaalouk DE., O'Brien S., Koivunen E., Arap W., Pasqualini R., Nakayama H., Kuniyasu A.
  • Journal Title: J. Biol. Chem. 283 Pages: 11752-11762
  • Peer Reviewed
• [Journal Article] Combinatorial targeting of the macropinocytotic pathway in leukemia and lymphoma cells. (2008)
  • Author(s): Nishimura S., et al.
  • Journal Title: J. Biol. Chem. 283 Pages: 11752-11762
  • Peer Reviewed
• [Presentation] 腫瘍選択的オートファジー誘導に基づく白血病治療薬の開発 (2010)
  • Author(s): 國安明彦, 西村真平, 中山仁
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 桃太郎アリーナ(岡山県)
  • Year and Date: 2010-03-29
• [Presentation] Notch-1 Fragment Peptide Induces Autophagy and Caspase-independent Cell Death in Leukemia Cell Lines (2010)
  • Author(s): 國安明彦, 西村真平, 中山仁
  • Organizer: AACR Special Conference "Cell Death Mechanisms and Cancer Therapy"
  • Place of Presentation: San Diego Omni Hotel(米国)
  • Year and Date: 2010-02-03
• [Presentation] 分泌性 Phospholipase A_2によるアディポサイトカイン産生制御 (2009)
  • Author(s): 萱島知子, 山田真梨子, 國安明彦
  • Organizer: 第26回日本薬学会九州支部大会
  • Place of Presentation: 九州大学(福岡県)
  • Year and Date: 2009-12-13
• [Presentation] ペプチドを利用したミクログリアへの特異的物質導入 (2009)
  • Author(s): 山中暢人, 谷口尊子, 川原浩一, 中山仁, 國安明彦
  • Organizer: 第26回日本薬学会九州支部大会
  • Place of Presentation: 九州大学(福岡県)
  • Year and Date: 2009-12-13
• [Presentation] 分泌性Phospholipase A2によるアディポサイトカイン産生制御 (2009)
  • Author(s): 萱島知子、山田真梨子、國安明彦
  • Organizer: 第26回日本薬学会九州支部大会
  • Place of Presentation: 九州大学(福岡県福岡市)
  • Year and Date: 2009-12-12
• [Presentation] 翻訳活性化を介した酸化LDLによるレジスチン産生促進 (2009)
  • Author(s): 萱島知子, 徳永真理子, 國安明彦, 杉本幸彦, 中山仁
  • Organizer: フォーラム2009衛生薬学・環境トキコロジー
  • Place of Presentation: 沖縄コンベンションセンター(沖縄県宜野湾市)
  • Year and Date: 2009-11-06
• [Presentation] アディポサイトカイン発現におけるホスホリパーゼA2修飾LDLの影響 (2009)
  • Author(s): 國安明彦, 萱島知子, 山田真梨子, 杉本幸彦
  • Organizer: フォーラム2009衛生薬学・環境トキコロジー
  • Place of Presentation: 沖縄コンベンションセンター(沖縄県宜野湾市)
  • Year and Date: 2009-11-05
• [Presentation] 翻訳活性化を介した酸化LDLによるレジスチン産生促進 (2009)
  • Author(s): 萱島知子, 徳永真理子, 國安明彦, 杉本幸彦, 中山仁
  • Organizer: フォーラム2009衛生薬学・環境トキシコロジー
  • Place of Presentation: 沖縄コンベンションセンター(沖縄県)
  • Year and Date: 2009-11-05
• [Presentation] アディポサイトカイン発現におけるホスホリパーゼA_2修飾LDLの影響 (2009)
  • Author(s): 國安明彦, 山田真梨子, 萱島知子, 杉本幸彦
  • Organizer: フォーラム2009衛生薬学・環境トキシコロジー
  • Place of Presentation: 沖縄コンベンションセンター(沖縄県)
  • Year and Date: 2009-11-05
• [Presentation] 細胞内導入キャリアとしてのミクログリア選択的ペプチドリガンド (2009)
  • Author(s): 山中暢人, 谷口尊子, 中山仁, 川原浩一, 杉本幸彦, 國安明彦
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド(兵庫県)
  • Year and Date: 2009-10-24
• [Presentation] 白血病細胞株における Notch 1由来ペプチド断片による非アポトーシス性細胞死誘導 (2009)
  • Author(s): 國安明彦, 佐藤直哉, 高橋俊輔, 杉本幸彦, 西村真平, 中山仁
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド(兵庫県)
  • Year and Date: 2009-10-23
• [Presentation] LANCL-1の細胞内局在と微小管関連分子としての役割 (2008)
  • Author(s): 瀬戸口 誠ら
  • Organizer: 第31回日本分子生物学年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] アディポネクチン発現におけるリゾホスファチジルコリンの作用 (2008)
  • Author(s): 萱島知子ら
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] アディポネクチン発現におけるリゾホスファチジルコリンの作用 (2008)
  • Author(s): 萱島知子, 國安明彦, 井上祥子
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートアイランド(兵庫県神戸市)
  • Year and Date: 2008-12-09
• [Presentation] 脂肪細胞における酸化ストレス誘発性PAI-1分泌の分子機序 (2008)
  • Author(s): 井上祥子, 徳永真理子, 國安明彦, 中山仁
  • Organizer: 第25回日本薬学会九州支部大会
  • Place of Presentation: 九州保健福祉大学(宮崎県延岡市)
  • Year and Date: 2008-12-07
• [Presentation] 脂肪細胞における酸化ストレス誘発性PAI-1分泌の分子機序 (2008)
  • Author(s): 井上祥子ら
  • Organizer: 日本薬学会第25回九州支部大会
  • Place of Presentation: 延岡
  • Year and Date: 2008-12-07
• [Presentation] アディポカイン発現によるリゾホスファチジルコリンの影響 (2008)
  • Author(s): 井上祥子, 國安明彦
  • Organizer: フォーラム2008衛生薬学・環境トキコロジー
  • Place of Presentation: 熊本市国際交流会館(熊本県熊本市)
  • Year and Date: 2008-10-17
• [Presentation] アディポカイン発現によるリゾホスファチジルコリンの影響 (2008)
  • Author(s): 井上祥子ら
  • Organizer: フォーラム2008衛生薬学・環境トキコロジー
  • Place of Presentation: 熊本
  • Year and Date: 2008-10-17
• [Remarks] ホームページ等
  • URL: http://square.umin.ac.jp/yseika/
• [Remarks]
  • URL: http://square.umin.ac.jp/yseika/
• [Patent(Industrial Property Rights)] オートファジー性細胞死を誘導するペプチド (2009)
  • Inventor(s): 國安明彦
  • Industrial Property Rights Holder: 熊本大学
  • Filing Date: 2009-03-25
  • Overseas