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The development and clinical application of a new oxidative stress marker using glutathionylated protein

新型谷胱甘肽氧化应激标记物的开发及临床应用

基本信息

批准号：
21590902
负责人：
IKEDA Satoshi
金额：
$ 2.91万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2012
项目状态：
已结题

项目摘要

Oxidative stress contributes to the development and progression of atherosclerosis. Reactive oxygen species, major sources of oxidative stress, modifies protein cysteine residues, where a disulfide bond is established between a cysteinyl residue and glutathione, leading to the S-glutathionylation of protein, and this modification can be still reversible. Therefore, we hypothesized a biomarker using S-glutathionylated protein is a good one reflecting an early phase of atherosclerosis. We composed the antibody against S-glutathionylation of apoprotein B100, a component of low-density lipoprotein (LDL) cholesterol. The serum values by immunoblot analysis with this antibody were correlated with negatively charged LDL subfractions, which are induced by oxidative modification, in patients with atherogenetic risks, such as hypertension, diabetes mellitus, and/or dyslipidemia. Immunohistological analysis of carotid endarterectomy sections with the antibody showed S-glutationylated ApoB100 localized at the site close to the vascular lumen, but not the site of foamy cell accumulation. These suggested that serum S-glutationylated ApoB100 may be an oxidative stress marker reflecting the relatively early phase of atherosclerosis.

氧化应激有助于动脉粥样硬化的发生和发展。活性氧是氧化应激的主要来源，它修饰蛋白质的半胱氨酸残基，在半胱氨酸残基和谷胱甘肽之间建立二硫键，导致蛋白质的s -谷胱甘肽化，这种修饰仍然是可逆的。因此，我们假设使用s -谷胱甘肽化蛋白作为生物标志物可以很好地反映动脉粥样硬化的早期阶段。我们合成了抗低密度脂蛋白（LDL）胆固醇成分载脂蛋白B100 s -谷胱甘肽化的抗体。在有动脉粥样硬化风险（如高血压、糖尿病和/或血脂异常）的患者中，用该抗体进行免疫印迹分析的血清值与氧化修饰诱导的负电荷LDL亚组分相关。用抗体对颈动脉内膜切除术切片进行免疫组织学分析，显示s -谷氨酸化的ApoB100定位在靠近血管腔的部位，而不是泡沫细胞聚集的部位。这表明血清s -谷氨酸化ApoB100可能是反映动脉粥样硬化相对早期阶段的氧化应激标志物。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Negatively charged low-density lipoprotein is associated with atherogenic risk in hypertensive patients

带负电荷的低密度脂蛋白与高血压患者的动脉粥样硬化风险相关

DOI：
10.1007/s00380-011-0139-z
发表时间：
2011
期刊：
Heart Vessels
影响因子：
1.5
作者：
Urata J;Ikeda S;Koga S;Nakata T;Yasunaga T;Sonoda K;Koide Y;Ashizawa N;Kohno S;Maemura K
通讯作者：
Maemura K

Is S-glutathionylated Apoprotein B100 a potential marker for atherogenic risk?

S-谷胱甘肽化脱辅基蛋白 B100 是动脉粥样硬化风险的潜在标志物吗？