Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Adv Exp Med Biol. 2010;662:49-55. doi: 10.1007/978-1-4419-1241-1_6.
Methylglyoxal (MG), a highly reactive alpha-oxoaldehyde generated by oxidation of carbohydrate and glycolysis, binds to proteins and forms advanced glycation end products (AGE). MG and MG adducts have been implicated in oxidative stress-related diseases, therefore, MG detoxifying system such as the glyoxalase system (glyoxalase I) also contributes to progression of these diseases. Recent papers have emphasized the pathophysiological effects of MG and the glyoxalase system in acute hypoxic injury, which is associated with acute oxidative stress. We investigated the kinetics of MG level and glyoxalase I activity in renal acute hypoxic injury induced by ischemia-reperfusion (I/R). I/R induced tubulointerstitial injury and the histological changes were associated with a significant decrease in renal glyoxalase I activity and an increase in MG level in the damaged tubular cells. Of note, rats over expressing human glyoxalase I showed amelioration of I/R-induced histological and functional damages and it was associated with a decrease in MG level in the lesion resulting in reduction of oxidative stress and tubular cell apoptosis. In conclusion, glyoxalase I has renoprotective effects in renal hypoxia such as I/R injury via a reduction in cytotoxic MG level in tubular cells.
甲基乙二醛（MG），一种由碳水化合物氧化和糖酵解产生的高度反应性α-氧代醛，与蛋白质结合形成晚期糖基化终产物（AGE）。MG 和 MG 加合物与氧化应激相关疾病有关，因此，MG 解毒系统（如醛糖还原酶系统（醛糖还原酶 I））也有助于这些疾病的进展。最近的论文强调了 MG 和醛糖还原酶系统在与急性氧化应激相关的急性缺氧损伤中的病理生理作用。我们研究了缺血再灌注（I / R）引起的肾脏急性缺氧损伤中 MG 水平和醛糖还原酶 I 活性的动力学。I / R 诱导肾小管间质损伤，组织学变化与肾醛糖还原酶 I 活性显著降低和损伤肾小管细胞中 MG 水平升高有关。值得注意的是，过表达人醛糖还原酶 I 的大鼠表现出 I / R 诱导的组织学和功能损伤的改善，这与病变中 MG 水平的降低有关，从而降低了氧化应激和肾小管细胞凋亡。总之，醛糖还原酶 I 通过降低肾小管细胞中细胞毒性 MG 水平，在肾脏缺氧（如 I / R 损伤）中具有肾保护作用。
