Ozone-oxidized cholesterols as biomarkers for metabolic syndrome and life-style related diseases

• Project/Area Number: 24300257
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Eating habits, studies on eating habits
• Research Institution: University of Shizuoka
• Principal Investigator: OHSHIMA Hiroshi 静岡県立大学, 食品栄養科学部, 教授 (80433209)
• Co-Investigator(Kenkyū-buntansha): MIYOSHI Noriyuki 静岡県立大学, 食品栄養科学部, 助教 (70438191) ; GODA Toshinao 静岡県立大学, 食品栄養科学部, 教授 (70195923) ; TOMONO Susumu 静岡県立大学, 食品栄養科学部, 客員研究員 (60554011) ; MIYOSHI Noriyuki 静岡県立大学, 食品栄養科学部, 客員教授 (00094342)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000); Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2012: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: 健康と食生活 / オゾン酸化コレステロール / 生活習慣病 / アルデヒド

Outline of Final Research Achievements

We have newly identified fatty-acid ester forms of secosterol-A including 9-oxononanoate secosterol-A and their secosterol-B derivatives as ozone-oxidized cholesterol fatty acid esters. These ester forms of secosterols were detected by a highly sensitive and specific LC-ESI-MS/MS method at 10~20 pmol/LDL mg protein in human low density lipoproteins obtained from healthy subjects. We further improved our method to analyze comprehensively various reactive aldehydes and carbonyls present in biological samples. We are currently using the method to study roles of reactive aldehydes and carbonyls in the development of various life-style related diseases such as arteriosclerosis, neurodegenerative diseases and cancer and also validate these reactive aldehydes including secosterols and unknowns as biomarkers for oxidative stress related disorders.

Research Products

• [Journal Article] Comprehensive analysis of the lipophilic reactive carbonyls present in biological specimens by LC/ESI-MS/MS (2015)
  • Author(s): Tomono S, Miyoshi N, Ohshima H
  • Journal Title: J Chromatogrphy B Volume: 988 Pages: 149-156
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Loss of p53 in stromal fibroblasts enhances tumor cell proliferation through nitric-oxide-mediated cyclooxygenase 2 activation (2015)
  • Author(s): Wada S, Matsushita Y, Tazawa H, Aoi, W Naito Y, HIgashi H, Ohshima H, Yoshikawa T
  • Journal Title: Free Radic Res Volume: 49 Issue: 3 Pages: 269-278
  • DOI: 10.3109/10715762.2014.997230
  • Peer Reviewed
• [Journal Article] Implications of cholesterol autoxidation products in the pathogenesis of inflammatory diseases (2014)
  • Author(s): Miyoshi N, Iuliano L, Tomono S, Ohshima H.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 446 Issue: 3 Pages: 702-708
  • DOI: 10.1016/j.bbrc.2013.12.107
  • Peer Reviewed
• [Journal Article] Occurrence of cytotoxic 9-oxononanoyl secosterol aldehydes in human low density lipoprotein. (2013)
  • Author(s): Miyoshi N, Iwasaki N, Tomono S, Higashi T, Ohshima H.
  • Journal Title: Free Radic.Biol.Med. Volume: 60 Pages: 73-79
  • DOI: 10.1016/j.freeradbiomed.2013.01.029
  • Peer Reviewed
• [Journal Article] Cytotoxic Effects of Secosterols and Their Derivatives on Several Cultured Cells (2013)
  • Author(s): Tomono S
  • Journal Title: Bioscience, Biotechnology, and Biochemistry Volume: 77 Issue: 3 Pages: 651-653
  • DOI: 10.1271/bbb.120758
  • NAID: 10031164790
  • ISSN: 0916-8451, 1347-6947
  • Peer Reviewed
• [Journal Article] Development and application of a method for identification of isothiocyanate-targeted molecules in colon cancer cells (2012)
  • Author(s): Miyoshi, N., Yonemochi, T., Tomono, S., Fukutomi, R., Nakamura, Y., Ohshima, H.
  • Journal Title: Anal. Biochem. Volume: 429(2) Issue: 2 Pages: 124-131
  • DOI: 10.1016/j.ab.2012.07.018
  • Peer Reviewed
• [Journal Article] Dysregulation of dimethylargininedimethylaminohydrolase/asymmetric dimethylarginine pathway in rat type II diabetic nephropathy (2012)
  • Author(s): Miyoshi N
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 51 Issue: 2 Pages: 143-149
  • DOI: 10.3164/jcbn.11-33
  • NAID: 130004879298
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed
• [Journal Article] Analysis of N^ε-ethyllysine in human plasma proteins by gas chromatography-negative ion chemical ionization/mass spectrometry as a biomarker for exposure to acetaldehyde and alcohol (2012)
  • Author(s): Mabuchi R., et al.
  • Journal Title: Alcohol.Clin.Exp.Res. Volume: (印刷中) Issue: 6 Pages: 1013-1020
  • DOI: 10.1111/j.1530-0277.2011.01705.x
  • Peer Reviewed
• [Journal Article] Inhibition of endothelial- and neuronal-type, but not inducible-type, nitric oxide synthase by the oxidized cholesterol metabolite secosterol aldehyde: Implications for vascular and neurodegenerative diseases (2011)
  • Author(s): Lai YL, Tomono S, Miyoshi N, Ohshima H
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 50 Issue: 1 Pages: 84-89
  • DOI: 10.3164/jcbn.11-31
  • NAID: 130004466675
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed
• [Presentation] 多層ナノチューブ肺内投与によって生じる活性カルボニル化合物の網羅的解析 (2014)
  • Author(s): 伴野勧、三好規之、徐結荀、津田洋幸、大島寛史
  • Organizer: 第67回日本酸化ストレス学会
  • Place of Presentation: 同志社大学、京都市
  • Year and Date: 2014-09-04 – 2014-09-05
• [Presentation] Denaturation of cellular proteins induced by secosterol aldehydes (2014)
  • Author(s): Noriyuki Miyoshi, Susumu Tomono, Hiroshi Ohshima.
  • Organizer: SFRR-international 2014
  • Place of Presentation: Kyoto,Japan
• [Presentation] Global analysis of reactive carbonyls formed in neuronal PC-12 cells by exposed to amyloid-beta (2014)
  • Author(s): Susumu Tomono, Misa Nagasawa, Noriyuki Miyoshi, Hiroshi Ohshima.
  • Organizer: SFRR-international 2014
  • Place of Presentation: Kyoto,Japan
• [Presentation] ob/obマウス糞便に含まれる起炎症性分子の探索 (2014)
  • Author(s): 眞田峻佑、大島寛史、三好規之
  • Organizer: 日本農芸化学会2014
  • Place of Presentation: 東京
• [Presentation] 植物ホルモン様ペプチドleginsulinの動物細胞に対する機能性解析 (2014)
  • Author(s): 坂野太研、伴野勧、大島寛史、三好規之、
  • Organizer: 日本農芸化学会2014
  • Place of Presentation: 東京
• [Presentation] KK-Ayマウスにおける山薬および有効成分ジオスゲニンの血中トリグリセライド低下作用 (2014)
  • Author(s): 三好規之、佐々木香、三浦信司、大島寛史
  • Organizer: 日本農芸化学会2014
  • Place of Presentation: 東京
• [Presentation] 神経細胞様分化PC-12へのamyloid-β曝露によって生成されるアルデヒド類の網羅的解析Comprehensive analysis of aldehydes formed in neuronal differenciated PC-12 cells by exposureto amyloid-β (2013)
  • Author(s): 長澤 美沙、伴野 勧、三好 規之、大島 寛史
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 横浜
• [Presentation] LC/ESI-MS/MSによる肥満・糖尿病モデルマウス（ob/ob）血漿中アルデヒドの網羅的解析Comprehensive analysis of aldehydes in obese/diabetes ob/ob mice plasma using LC/ESI-MS/MS (2013)
  • Author(s): 伴野勧、長澤美沙、村田晴美、眞田峻介、三好規之、大島寛史
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 横浜
• [Presentation] Cholesterol aldehydes: The mechanisms of their formation and pahological roles in oxidative stress related-disorders (2013)
  • Author(s): Noriyuki Miyoshi, Susumu Tomono, Hiroshi Ohshima.
  • Organizer: 3rd European Network for Oxysterol Research
  • Place of Presentation: Swansea, UK
• [Presentation] Conprehensive analytical method for lipophilic reactive carbonyl compounds in biological samples (2013)
  • Author(s): Susumu Tomono, Noriyuki Miyoshi, Hiroshi Ohshima.
  • Organizer: SFRR-Europe 2013 Conference
  • Place of Presentation: Athens, Greece
• [Presentation] Acetaldehyde-modification of dehydrogenase/reductase member 2 decrease its binding to Mdm2 (2013)
  • Author(s): Yuji Yamada, Aya Kurita, Susumu Tomono, Noriyuki Miyoshi, Hiroshi Ohshima.
  • Organizer: 静岡健康・長寿学術フォーラム
  • Place of Presentation: 静岡
• [Presentation] Identification of carcinogenic compounds formed by chronic ethanol feeding in feces of mice (2013)
  • Author(s): Shoko Hirukawa, Shunsuke Sanada, Noriyuki Miyoshi, Hiroshi Ohshima.
  • Organizer: 静岡健康・長寿学術フォーラム
  • Place of Presentation: 静岡
• [Presentation] Search as novel diagnostic biomarkers for fecal small molecules responsible for metabolic syndrome in ob/ob mice (2013)
  • Author(s): Shunsuke Sanada, Shoko Hirukawa, Noriyuki Miyoshi, Hiroshi Ohshima.
  • Organizer: 静岡健康・長寿学術フォーラム
  • Place of Presentation: 静岡
• [Presentation] 青大豆に含まれる植物ホルモン様ペプチドleginsulinの解析 (2013)
  • Author(s): 坂野太研、三好規之、池本裕之、今井伸二郎、大島寛史
  • Organizer: JSoFF 2013
  • Place of Presentation: 東京
• [Presentation] 食後の血中脂質に対するヤムイモおよびその含有成分ジオスゲニンの効果 (2013)
  • Author(s): 三好規之、平田隼、新井英一、大島寛史
  • Organizer: 日本農芸化学会2013
  • Place of Presentation: 仙台
• [Presentation] ob/obマウス糞便抽出物の分析によるメタボリック症候群新規診断バイオマーカーの探索 (2013)
  • Author(s): 眞田峻佑、蛭川頌子、大島寛史、三好規之
  • Organizer: 日本農芸化学会2013
  • Place of Presentation: 仙台
• [Presentation] 飲酒によって変動するマウス糞便中化合物の探索 (2013)
  • Author(s): 蛭川頌子、眞田峻佑、大島寛史、三好規之
  • Organizer: 日本農芸化学会2013
  • Place of Presentation: 仙台
• [Presentation] オゾン酸化コレステロール : 生成機構、生理活性および生活習慣病発症における役割 (2012)
  • Author(s): 大島寛史、伴野勧、頼盈伶、三好規之
  • Organizer: 第65回日本酸化ストレス学会
  • Place of Presentation: 徳島
• [Presentation] 肥満モデルマウスKK-Ayにおける山薬およびジオスゲニンの大腸発がん予防分子機構解析 (2012)
  • Author(s): 三好規之、長澤友樹、田中卓二、若林敬二、大島寛史
  • Organizer: がん予防学会2012
  • Place of Presentation: 岐阜
• [Presentation] 糖尿病モデルラット肝におけるDNA付加体の網羅的解析 (2012)
  • Author(s): 三好規之、松田知成、大島寛史
  • Organizer: 第71回日本癌学会
  • Place of Presentation: 札幌
• [Presentation] Dehydrogenase/reductase member 2 (DHRS2)におけるアセトアルデヒド修飾はMdm2との結合を減少させる (2012)
  • Author(s): 山田雄司、三好規之、大島寛史
  • Organizer: 第71回日本癌学会
  • Place of Presentation: 札幌
• [Presentation] ヒトがん細胞におけるイソチオシアネート結合分子の網羅的解析 (2012)
  • Author(s): 米持巧、中村宜督、大島寛史、三好規之
  • Organizer: 第17回日本フードファクター学会
  • Place of Presentation: 静岡
• [Presentation] ジオスゲニンおよび山薬による食後高トリグリセライド血症の抑制効果 (2012)
  • Author(s): 平田隼、三好規之、新井英一、大島寛史
  • Organizer: 第17回日本フードファクター学会
  • Place of Presentation: 静岡
• [Presentation] 日本のヤマイモ類及びその植物ステロイド成分によるマウス大腸発がんの予防 (2012)
  • Author(s): Hiroshi Ohshima, Tomoki Nagasawa, Natsuko Asai, Noriyuki Miyoshi, Keiji Wakabayashi, Takuji Tanaka
  • Organizer: The 1st International Conference on Pharma-Food
  • Place of Presentation: 静岡
• [Presentation] 飲酒およびアセトアルデヒド曝露のバイオマーカーとしてのタンパク質中Nε-エチルリジンの有用性 (2012)
  • Author(s): Ryota Mabuchi, Noriyuki Miyoshi, Akira Yokoyama, Yoshihide Suwa, Kiyonari Kuriki, Toshinao Goda, Takashi Amagai, Hiroshi Ohshima
  • Organizer: 日本環境変異原学会第41回大会
  • Place of Presentation: 静岡
• [Presentation] がん予防食品因子イソチオシアネート結合タンパク質の網羅的探索法 (2012)
  • Author(s): 三好規之、米持巧、伴野勧、中村宜督、大島寛史
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 博多
• [Presentation] LC-ESI-MS/MSを用いた脂質過酸化物由来アルデヒド化合物の網羅的解析法の開発 (2012)
  • Author(s): 伴野勧、村田晴美、大畑美幸、三好規之、大島寛史
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 博多
• [Presentation] Dehydrogenase/reductase member 2 のアセトアルデヒド修飾はMdm2結合活性を低下させる (2012)
  • Author(s): 山田雄司、三好規之、伴野勧、大島寛史
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 博多
• [Book] CANCER AND INFLAMMATION MECHANISMS Chemical, Biological and Clibical Asdpects (2014)
  • Author(s): Hiraku Y, Kawanishi S, Ohshima H
  • Total Pages: 383
  • Publisher: John Wiley & Sons
• [Book] 酸化ストレスの医学 (2014)
  • Author(s): 大島寛史。三好規之、伴野勧
  • Publisher: 診断と治療社
• [Book] 基礎生化学-健康・疾病とのつながり- (2013)
  • Author(s): 永井竜児、大島寛史(編)
  • Total Pages: 259
  • Publisher: アイ・ケイ コーポレーション
• [Remarks]
  • URL: http://sfns.u-shizuoka.ac.jp/cellbioc/index.html