Mera Katsumi, Fujiwara Yukio, Otagiri Masaki, Sakata Noriyuki, Nagai Ryoji
Department of Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
Ann N Y Acad Sci. 2008 Apr;1126:155-7. doi: 10.1196/annals.1433.000. Epub 2007 Dec 13.
N omega-(carboxymethyl)arginine (CMA) is an acid-labile advanced glycation end product (AGE) that was discovered in enzymatic hydrolysate of glycated collagen. Subsequently, CMA was also detected in human serum, and its level in patients with diabetes was found to be higher than in people without the disease. However, the histological localization of CMA and its pathophysiological significance remains poorly understood. Here, to address this issue, we developed a monoclonal antibody specific for CMA. This antibody reacted with CMA and CMA-protein adduct, whereas it did not cross-react with its analogues, such as N epsilon-(carboxymethyl)lysine and S-(carboxymethyl)cysteine, indicating that the antibody specifically recognizes CMA. Upon immunohistochemical analysis, a significant CMA immnoreactivity was found in atherosclerotic lesions, whereas no such immunoreactivity was observed in normal regions. This suggests that the accumulation of CMA in tissue proteins may contribute to the pathophysiologies associated with aging and age-related diseases.
Nω-（羧甲基）精氨酸（CMA）是一种对酸不稳定的晚期糖基化终产物（AGE），它是在糖化胶原蛋白的酶解产物中发现的。随后，在人血清中也检测到了CMA，并且发现糖尿病患者体内的CMA水平高于非糖尿病患者。然而，CMA的组织学定位及其病理生理学意义仍知之甚少。在此，为了解决这个问题，我们开发了一种针对CMA的单克隆抗体。该抗体与CMA和CMA-蛋白质加合物发生反应，而不与其类似物如Nε-（羧甲基）赖氨酸和S-（羧甲基）半胱氨酸发生交叉反应，这表明该抗体能特异性识别CMA。免疫组织化学分析显示，在动脉粥样硬化病变中存在显著的CMA免疫反应性，而在正常区域未观察到这种免疫反应性。这表明CMA在组织蛋白中的积累可能与衰老及年龄相关疾病的病理生理学有关。
