Division of Chemical Metrology and Analytical Science, National Institute of Metrology, Beijing 100013, P.R. China.
School of Life Science, Beijing Institute of Technology, Beijing 100081, P.R. China.
Int J Mol Med. 2014 Mar;33(3):736-42. doi: 10.3892/ijmm.2013.1604. Epub 2013 Dec 24.
There are statistical data indicating that diabetes is a risk factor for Parkinson's disease (PD). Methylglyoxal (MG), a biologically reactive byproduct of glucose metabolism, the levels of which have been shown to be increase in diabetes, reacts with dopamine to form 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (ADTIQ); this formation may provide further insight into the connection between PD and diabetes. In this study, we investigated the role of ADTIQ in these two diseases to determine in an aim to enhance our understanding of the link between PD and diabetes. To this end, a cell model of hyperglycemia and a rat model of diabetes were established. In the cell model of hyperglycemia, compared with the control group, the elevated glucose levels promoted free hydroxyl radical formation (p<0.01). An ADTIQ assay was successfully developed and ADTIQ levels were detected and quantified. The levels of its precursors, MG and dopamine (DA), were determined in both the cell model of hyperglycemia and the rat model of diabetes. The proteins related to glucose metabolism were also assayed. Compared with the control group, ADTIQ and MG levels were significantly elevated not only in the cell model of hyperglycemia, but also in the brains of rats with diabetes (p<0.01). Seven key enzymes from the glycolytic pathway were found to be significantly more abundant in the brains of rats with diabetes. Moreover, it was found that adenosine triphosphate (ATP) synthase and superoxide dismutase (SOD) expression levels were markedly decreased in the rats with diabetes compared with the control group. Therefore, ADTIQ expression levels were found to be elevated under hyperglycemic conditions. The results reported herein demonstrate that ADTIQ, which is derived from MG, the levels of which are increased in diabetes, may serve as a neurotoxin to dopaminergic neurons, eventually leading to PD.
有统计数据表明，糖尿病是帕金森病（PD）的一个风险因素。甲基乙二醛（MG）是葡萄糖代谢的生物反应副产物，其水平已被证明在糖尿病中增加，与多巴胺反应形成 1-乙酰基-6,7-二羟基-1,2,3,4-四氢异喹啉（ADTIQ）；这种形成可能为 PD 与糖尿病之间的联系提供更多的深入了解。在这项研究中，我们研究了 ADTIQ 在这两种疾病中的作用，目的是增强我们对 PD 和糖尿病之间联系的理解。为此，建立了高血糖细胞模型和糖尿病大鼠模型。在高血糖细胞模型中，与对照组相比，升高的葡萄糖水平促进了游离羟基自由基的形成（p<0.01）。成功开发了 ADTIQ 测定法，并检测和定量了 ADTIQ 水平。在高血糖细胞模型和糖尿病大鼠模型中测定了其前体 MG 和多巴胺（DA）的水平。还测定了与葡萄糖代谢相关的蛋白质。与对照组相比，不仅在高血糖细胞模型中，而且在糖尿病大鼠的大脑中，ADTIQ 和 MG 水平均显著升高（p<0.01）。发现糖酵解途径中的 7 种关键酶在糖尿病大鼠的大脑中明显更为丰富。此外，与对照组相比，发现糖尿病大鼠的三磷酸腺苷（ATP）合酶和超氧化物歧化酶（SOD）表达水平明显降低。因此，在高血糖条件下发现 ADTIQ 的表达水平升高。本报告所述的结果表明，ADTIQ 可能是一种神经毒素，作用于多巴胺能神经元，最终导致 PD，其来源于糖尿病中增加的 MG。
