Faculty of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, Akibaku, Niigata, 956-0841, Japan.
Toita Women's College, Minatoku, Tokyo, 105-0014, Japan.
Biochimie. 2020 Dec;179:69-76. doi: 10.1016/j.biochi.2020.09.010. Epub 2020 Sep 16.
One hypothesis regarding the cause of diabetic complications is that advanced glycation end products (AGEs) bind to the AGE receptor and induce changes in gene expression. However, what AGEs exist in vivo and how individual AGEs are produced and impact body metabolic process to cause diabetes complications are not understood. We developed a new precise method to measure AGEs using LC-MS/MS with a new column and measured 7 free AGEs, including N(6)-carboxymethyllysine (CML), N(6)-(1-carboxyethyl)-l-lysine (CEL) and N5-(5-hydro-5-methyl-4-imidazolon-2-yl)L-ornithine (MG-H1), in human blood components. Blood was obtained from 9 people, and free AGEs were measured in individual blood components with LC-MS/MS before and after a meal. Free CML and CEL were abundant in erythrocytes, with 92% of free CML and 85% of free CEL localized in erythrocytes. In contrast, 60% of free MG-H1 was distributed in the serum. After the meal, free serum MG-H1 increased, but CML and CEL did not. CML and CEL are mainly distributed in erythrocytes and were not affected by the meal, indicating that they are produced in vivo. However, the main source of MG-H1 is the meal. The effect of genetic polymorphisms on AGEs was also investigated. Low activity type aldehyde dehydrogenase 2 (ALDH2) increased the CML concentration in the blood. This is the first observation that shows that the metabolic process of CML and CEL is different from that of MG-H1 and the effect of ALDH2 SNPs on CML.
关于糖尿病并发症原因的一个假设是，糖基化终产物（AGEs）与 AGE 受体结合，诱导基因表达的改变。然而，体内存在哪些 AGEs，以及个体 AGEs 是如何产生的，以及如何影响身体代谢过程导致糖尿病并发症，目前尚不清楚。我们开发了一种使用 LC-MS/MS 结合新柱的新精确方法来测量 AGEs，并测量了 7 种游离 AGEs，包括 N(6)-羧甲基赖氨酸（CML）、N(6)-(1-羧乙基)-L-赖氨酸（CEL）和 N5-(5-氢-5-甲基-4-咪唑啉-2-基）L-鸟氨酸（MG-H1），在人血成分中。从 9 个人中采集血液，并使用 LC-MS/MS 在餐前和餐后分别测量个体血液成分中的游离 AGEs。游离 CML 和 CEL 在红细胞中含量丰富，游离 CML 中有 92%，游离 CEL 中有 85%定位于红细胞中。相比之下，60%的游离 MG-H1 分布在血清中。餐后，游离血清 MG-H1 增加，但 CML 和 CEL 没有增加。CML 和 CEL 主要分布在红细胞中，不受膳食影响，表明它们是在体内产生的。然而，MG-H1 的主要来源是膳食。还研究了遗传多态性对 AGEs 的影响。低活性型乙醛脱氢酶 2（ALDH2）增加了血液中的 CML 浓度。这是首次观察到 CML 和 CEL 的代谢过程不同于 MG-H1，以及 ALDH2 SNP 对 CML 的影响。
