Involvement of Oxygen Radicals in Aging

氧自由基参与衰老

• 批准号: 04836005
• 负责人: YAMAMOTO Yorihiro
• 金额: $ 1.15万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04836005/
• 关键词: Lipid Peroxides; Free Fatty Acid Oxidation Products; Oxygen Radicals; Oxidative Stress; リン脂質過酸化物

It is considered that oxygen radicals should be involved in the aging process since the life time of species inversely correlates with metabolic rates of them. One of the direct evidence for the oxidative damage of the tissue is the presence of cholesteryl ester hydroperoxide in normal human plasma. This hydroperoxide levels in rat plasmas are higher than those in humans. This results indicate the positive correlation between the oxidative stress and aging. It is also interesting that analbuminemic rats, which is very susceptible to the induction of cancers by certain amines, have higher hydroperoxide levels.Next I could develop the method for the detection of hydroperoxides of phospholipids such as phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and cardiolipin. However, no phospholipid hydroperoxides were detected in rat liver and heart. This is likely due to the reduction of the hydroperoxides by glutathione peroxidase.Therefore, it is necessary to detect the oxidation products of free fatty acids. It is found that the derivatization of them by monodansylcadaverine is very useful for the picomole level detection and one of the oxidation products increased in the rats under oxidative stress.

由于物种的寿命与其代谢率呈负相关，因此认为氧自由基应参与衰老过程。组织氧化损伤的直接证据之一是正常人血浆中存在胆固醇酯氢过氧化氢。这种氢过氧化氢在大鼠血浆中的水平高于人类。这一结果表明氧化应激与衰老呈正相关。同样有趣的是，高蛋白血症大鼠对某些胺的致癌非常敏感，其过氧化氢水平较高。下一步，我可以开发出检测磷脂酰乙醇胺、磷脂酰丝氨酸、磷脂酰肌醇和心磷脂等磷脂过氧化氢的方法。而在大鼠肝脏和心脏中未检测到磷脂过氧化产物。这可能是由于谷胱甘肽过氧化物酶还原过氧化氢所致，因此，有必要对游离脂肪酸的氧化产物进行检测。研究发现，单丹西维林对它们的衍生化非常有用，在氧化应激大鼠体内，其中一种氧化产物增加了皮摩尔的水平。

项目成果

Y.Nagata, Y.Yamamoto, S.Yamamoto, and E.Niki: "Fluorometric analysis of free fatty acid hydroperoxides and their alcohols, and its application to blood plasma." in "Oxygen Radicals" eds.by K.Yagi, M.Kondo, E.Niki, and T.Yoshikawa, Elsevier. 315-318 (1992)

Y.Nagata、Y.Yamamoto、S.Yamamoto 和 E.Niki：“游离脂肪酸氢过氧化物及其醇的荧光分析及其在血浆中的应用。”

Y.Yamamoto, Y.Nagata, E.Niki, K.Watanabe, and S.Yoshimura: "Plasma glutathione peroxidase reduces phosphatidylcholine hydroperoxide." Biochem.Biophys.Res.Commun.193. 133-138 (1993)

Y.Yamamoto、Y.Nagata、E.Niki、K.Watanabe 和 S.Yoshimura：“血浆谷胱甘肽过氧化物酶可减少氢过氧化磷脂酰胆碱。”

Y.Yamamoto: "Comparison of Plasma Levels of Lipid Hydroperoxides and Antioxidants in Hyperlipidemic Nagr〓e Analbuminemic Rats,Sprague Dawley Rats,and Humans" Biochem.Biophys.Res.Commun.189. 518-523 (1992)

Y. Yamamoto：“高脂血症 Nagr〓e 无白蛋白血症大鼠、Sprague Dawley 大鼠和人类血浆中脂质氢过氧化物和抗氧化剂的水平比较”Biochem.Biophys.Res.Commun.189 (1992)。

Y.Yamamoto: "Method for the Detection of Phospholipid Hydroperoxides at Pi〓〓mole Levels and its Application to Biological Samples" Oxygen Radicals. 311-314 (1992)

Y. Yamamoto：“Pi〓〓摩尔水平磷脂氢过氧化物的检测方法及其在生物样品中的应用”氧自由基 311-314 (1992)。

C.Naito: "Lipid peroxides as the initiating factor of atherosclerosis" Ann.New York Acad.Sci.676. 27-45 (1993)

C.Naito：“脂质过氧化物是动脉粥样硬化的引发因素”Ann.New York Acad.Sci.676。