Analysis and Protection on Oxidative stress in Vascular Systems

在生命系统中，氧化应激被认为是由包括脂质过氧化物在内的活性氧诱导的。特别是血液系统氧化应激是动脉粥样硬化和血栓形成的主要原因之一。谷胱甘肽过氧化物酶、过氧化氢酶和超氧化物歧化酶对氧化应激具有重要的抗氧化保护作用。今年，我们研究了脂质过氧化产物，特别是4-羟基壬烯醛对红细胞的影响。与4-羟基壬烯醛反应后，红细胞中谷胱甘肽含量降低，碳酸酐酶等含有SH基团的酶被破坏。我们还研究了自由基在糖尿病中的作用。近年来，我们发现一些生物标志物如羧甲基赖氨酸（CML）和8-羟基脱氧鸟苷预先排泄到糖尿病患者的尿液中。我们还发现糖尿病患者血液中存在新型晚期糖基化终产物，称为MRX和MRY。兔、羊红细胞与葡萄糖反应可产生MRX和MRY，并发现精氨酸和半胱氨酸作为MRX和MRY的前体发挥重要作用。化学分析对结构的解释正在取得进展。

In the living system, oxidative stress is supposed to be induced by active oxygens including lipid-peroxides. In perticular, oxidative stress caused in blood systems is one of the major reason for atherosclerosis and thrombosis. Glutathione-peroxidase, catalase and superxide-dismutase play an important role for antioxidative ptotection from oxidative stress. This year, we examined the effect of lipid peroxidation products, in particular 4-hydroxynonenal on erythrocytes. Glutathione contents in erythrocytes were decreased by the reaction with 4-hydroxynonenal, and it was found that several enzymes which have SH groups such as carbonic anhydrase were found to be damaged. We have also been involved in the involvement of free radicals in diabetes. Recently we found that several biomarkers such as carboxymethyllysine (CML) and 8-hydroxydeoxyguanosine are prexcreted into urine of diabete patients. We also found that novel type of advanced glycation end products are present in blood of diabete patients, which were named as MRX and MRY.MRY and MRY can be produced by the reaction of erythrocytes of rabbit and sheep with glucose, and it was found that arginine and cysteine play an important role as the precursor of MRX and MRY.Chemical analyzes for structure elucidation is now progress.