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Elucidation of a novel relationship between the oxidative stress-related products and common diseases

阐明氧化应激相关产物与常见疾病之间的新关系

基本信息

批准号：
16590054
负责人：
KUNIYASU Akihiko
金额：
$ 2.3万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

Adipocytokines such as adiponectin, leptin and resistin are hormone-like molecules that secreted from adipocytes. Recently oxidative stress has been reported to be associated to the abnormality of adipocytokine secretion, which evokes the metabolic syndrome. Previously we found that adipose CD36 functioning as a long-fatty acid transporter plays an role in clearance of oxidized low density lipoprotein (OxLDL) and advanced glycation end products (AGE)-modified molecules.In this study, we examined the effect of OxLDL and AGEs on adipocytekine secretions in 3T3-L1 adipose cells. First of all, both OxLDL and AGIE-BSA down-regulated the leptin expression via generation of active oxygen species. Second OxLDL up-regulated the plasminogen activator inhibitor-1 (PAI-1), which is a risk factor of atherosclerosis. We also demonstrated that lysophosphatidylcholine, which is a major phospholipids component of OxLDL, stimulates the PAI-1 mRNA expression via generation of ROS, resulting in an increasing of PAI-1 secretion. In addition, resistin, which evokes the insulin resistance, was up-regulated by the treatment of OxLDL on 3T3-L1 adipocytes. Polysome analysis revealed that OxLDL stimulated the protein translation of resistin mRNA. We also searched the major component of the resistin expression stimulator in OxLDL and found several fractions of the lipid peroxides.Consequent y we demonstrated that OxLDL stimulated the expression of both PAI-1 and resistin, and OxLDL and AGE-BSA reduced the expression of leptin. These results suggest oxidative stress-related products may alter the expression of adipocytokines, which involved n the metabolic syndromes. Further elucidation of the molecular mechanism by which OxLDL induces abnormality of adipocytokine secretion may shed light on a new aspect of metabolic syndromes and lead to the development of drug for the common diseases.

脂肪细胞因子如脂联素、瘦素和抵抗素是由脂肪细胞分泌的激素样分子。最近有报道称氧化应激与脂肪细胞因子分泌异常有关，引起代谢综合征。先前我们发现脂肪CD36作为长脂肪酸转运体在氧化低密度脂蛋白（OxLDL）和晚期糖基化终产物（AGE）修饰分子的清除中起作用。在这项研究中，我们检测了OxLDL和AGEs对3T3-L1脂肪细胞中脂肪细胞因子分泌的影响。首先，OxLDL和AGIE-BSA均通过活性氧的产生下调瘦素的表达。第二，OxLDL上调纤溶酶原激活物抑制剂-1 (PAI-1)，这是动脉粥样硬化的危险因素。我们还证明，溶血磷脂酰胆碱是OxLDL的主要磷脂成分，通过生成ROS刺激PAI-1 mRNA表达，导致PAI-1分泌增加。此外，引起胰岛素抵抗的抵抗素通过OxLDL处理3T3-L1脂肪细胞而上调。多体分析显示，OxLDL刺激了抵抗素mRNA的蛋白翻译。我们还在OxLDL中搜索了抵抗素表达刺激因子的主要成分，发现了一些脂质过氧化物。随后，我们证明OxLDL刺激PAI-1和抵抗素的表达，OxLDL和AGE-BSA降低瘦素的表达。这些结果表明，氧化应激相关产物可能会改变脂肪细胞因子的表达，这与代谢综合征有关。进一步阐明OxLDL诱导脂肪细胞因子分泌异常的分子机制，可能为代谢综合征的研究提供新的视角，并为常见疾病的药物开发提供指导。

项目成果

期刊论文数量（22）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Advanced glycation end products-modified proteins and oxidized LDL mediate down-regulation of leptin in mouse adipocytes via CD36

高级糖基化终末产物修饰蛋白和氧化 LDL 通过 CD36 介导小鼠脂肪细胞中瘦素的下调

DOI：
发表时间：
2004
期刊：
Biochem.Biophys.Res.Commun 325
影响因子：
0
作者：
Vanier MT;Saito Y;Murayama S;Suzuki K;Suzuki S et al.;Suzuki S et al.;Suzuki S et al.;TOMOHITO GOHDA;Nakano N et al.;Alderson NL et al.;Liu SX et al.;Matsunaga N et al.;Nagai R et al.;Waanders F et al.;Greven WL et al.;Morita K et al.;永井竜児ら;永井竜児ら;Morita K et al.;Nagai R et al.;Koito W et al.;Unno Y et al.
通讯作者：
Unno Y et al.

Glycolaldehyde-modified bovine serum albumin downregulates leptin expression in mouse adipocytes via a CD36-mediated pathway

乙醇醛修饰的牛血清白蛋白通过 CD36 介导的途径下调小鼠脂肪细胞中瘦素的表达

DOI：
发表时间：
2005
期刊：
Ann. N.Y. Acad. Sci. 1043
影响因子：
0
作者：
Y.Unno;M.Sakai;Y.Sakamoto;A.Kuniyasu;R.Nagai;H.Nakayama;S.Horiuchi
通讯作者：
S.Horiuchi

Characterization of benzodiazepine binding site on human al-acid glycoprotein using flunitrazepam as a photolabeling agent

使用氟硝西泮作为光标记剂表征人 α-酸性糖蛋白上的苯二氮卓结合位点

DOI：
发表时间：
2005
期刊：
Biochim. Biophys. Acta 1725
影响因子：
0
作者：
V.T.Chuang;M.Hijioka;M.Katsuki;K.Nishi;T.Hara;K.I.Kaneko;M.Ueno;A.Kuniyasu;H.Nakayama;M.Otagiri
通讯作者：
M.Otagiri

Glycolaldehyde-modified bovine serum albumin downregulates leptin expression in mouse adipocytes via a CD36- mediated pathway

乙醇醛修饰的牛血清白蛋白通过 CD36 介导的途径下调小鼠脂肪细胞中瘦素的表达