Identification of inflammation-mediated oxidized cholesterols as novel biomarkers of the metabolic syndrome

鉴定炎症介导的氧化胆固醇作为代谢综合征的新型生物标志物

• 批准号: 18509001
• 负责人: OHSHIMA Hiroshi
• 金额: $ 2.17万
• 依托单位: University of Shizuoka
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18509001/
• 关键词: cholesterol; reactive oxygen and nitrogen species; metabolic syndrome; chronic inflammation; ozone

The metabolic syndrome is a risk factor for atherosclerosis. Adipocytokines produced by fat cells may activate various inflammatory cells to produce reactive oxygen and nitrogen species, which play important roles in host defenses against pathogens as well as in tissue damage in inflamed tissues. It has recently been reported that human activated neutrophils produce an ozone-like oxidant (s) in vivo, but conflicting experimental results have also been reported. In the present study in order to establish whether human inflammatory cells produce the ozone-like oxidant in vivo, we have investigated the followings using atheronal-A and B, which are oxidized-cholesterols specifically produced by the reaction with ozone: (1) synthesis and characterization of atheronal-A and B, (2) development of a highly sensitive and specific method to detect atheronal-A and B using fluorescent dansyl hydrazine derivatives, (3) elucidation of the mechanism for the formation of atheronal-A and B and also ozo … More ne-like oxidant (s) in vivo by inflammatory cells, (4) biological activities, especially ability to induce apoptotic cell death, and(5)detection of atheronal-A and B in tissues such as the liver of diabetes rats. Our developed method is about one thousand times more sensitive than the previously reported methods and can detect fmol levels of the compounds easily. Using this method, we have shown that increased levels of atheronal-B were formed in human neutrophil-like (HL-60) cells activated with phorbolester, compared to those without activation. As the formation of atheronal-B was inhibited specifically by a compound which inhibits ozone-mediated oxidation, our data strongly suggest that ozone produced by the activated HL-60 is involved in the formation of atheronals. It was also shown that atheronals exhibited strong cytotoxicity. As we also detected elevated levels of atheronals in the liver of diabetes rats, the compounds could be measured as a novel marker for the metabolic syndrome. Less

代谢综合征是动脉粥样硬化的危险因素。脂肪细胞产生的脂肪细胞因子可以激活各种炎症细胞产生活性氧和氮，这在宿主防御病原体以及炎症组织的组织损伤中发挥重要作用。最近有报道称，人类活化的中性粒细胞在体内产生类似臭氧的氧化剂，但也有相互矛盾的实验结果报道。在本研究中，为了确定人类炎症细胞是否在体内产生类臭氧氧化剂，我们使用 atheronal-A 和 B（它们是与臭氧反应专门产生的氧化胆固醇）进行了以下研究：（1）atheronal-A 和 B 的合成和表征，（2）开发一种使用荧光丹磺酰检测 atheronal-A 和 B 的高灵敏度和特异性方法 肼衍生物，（3）阐明炎症细胞在体内形成动脉粥样硬化A和B以及臭氧样氧化剂的机制，（4）生物活性，特别是诱导细胞凋亡的能力，以及（5）在糖尿病大鼠肝脏等组织中检测动脉粥样硬化A和B。我们开发的方法比之前报道的方法灵敏约一千倍，并且可以轻松检测化合物的 fmol 水平。使用这种方法，我们发现，与未激活的细胞相比，用佛波酯激活的人中性粒细胞样 (HL-60) 细胞中形成的动脉粥样硬化 B 水平增加。由于 atheronal-B 的形成受到抑制臭氧介导的氧化的化合物的特异性抑制，因此我们的数据强烈表明由活化的 HL-60 产生的臭氧参与了 atheronal 的形成。还表明动脉粥样硬化分子表现出强烈的细胞毒性。由于我们还在糖尿病大鼠的肝脏中检测到动脉粥样硬化水平升高，因此这些化合物可以作为代谢综合征的新标志物进行测量。较少的

项目成果

The role of nitrative DNA damage in inflammation-associated

硝基 DNA 损伤在炎症相关疾病中的作用

• 发表时间: 2007
• 作者: Ohshima;H.;Sawa;T.;Tazawa;H.;Kawanishi;S
• 通讯作者: S

Helicobacter pylori Infection, Oxidative and Nitrative Stress and Stomach Cancer

幽门螺杆菌感染、氧化和硝化应激与胃癌

• 发表时间: 2007
• 作者: Ohshima;H.;Sawa;T.;Tatemichi;M.;Bancel;B.;Pignatelli;B
• 通讯作者: B

リーブ葉エキス含有食品の抗酸化性、血糖値低減およびAGEs生成抑制効果

含有叶提取物的食物的抗氧化特性、降低血糖水平和抑制 AGEs 产生的作用

• 发表时间: 2007
• 期刊: 健康・栄養食品研究 10
• 作者: 佐々木 裕、増田 修一;他
• 通讯作者: 他

Cholesterol ozonolysis products as a possible biomarker for metabolic syndrome.

胆固醇臭氧分解产物作为代谢综合征的可能生物标志物。

• 发表时间: 2008
• 作者: Tomono S.;Iwabuchi T.;Yasue Y.;Niizuma S.;Miyoshi M.;Ohshima H.
• 通讯作者: Ohshima H.

Geographic distribution of liver and stomach cancers in Thailand in relation to estimated dietary intake of nitrate, nitrite, and nitrosodimethylamine

• DOI: 10.1080/01635580701649636
• 发表时间: 2008-03-01
• 期刊: NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
• 影响因子: 2.9
• 作者: Mitacek, Eugene J.;Brunnemann, Klaus D.;Martin, Nimit
• 通讯作者: Martin, Nimit