Formation of a salsolinol-like compound, the neurotoxin, 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, in a cellular model of hyperglycemia and a rat model of diabetes.
Formation of a salsolinol-like compound, the neurotoxin, 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, in a cellular model of hyperglycemia and a rat model of diabetes.
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DOI：
10.3892/ijmm.2013.1604
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发表时间：
2014-03
影响因子：
5.4
通讯作者：
Dewei Song;Nian Xin;B. Xie;Yu-juan Li;Ling-Yan Meng;Hong-mei Li;M. Schläppi;Yu-lin Deng
中科院分区：
文献类型：
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作者：
Dewei Song;Nian Xin;B. Xie;Yu-juan Li;Ling-Yan Meng;Hong-mei Li;M. Schläppi;Yu-lin Deng
有统计数据表明，糖尿病是帕金森病(PD)的危险因素。甲基乙二醛(MG)是葡萄糖代谢的一种生物活性副产物，其水平在糖尿病时会增加，它与多巴胺反应生成1-acetyl-6，7-dihydroxy-1，2，3，4-tetrahydroisoquinoline(ADTIQ)，这种形成可能为进一步了解PD与糖尿病之间的联系提供依据。在这项研究中，我们调查了ADTIQ在这两种疾病中的作用，以确定目的是为了加强我们对PD和糖尿病之间的联系的理解。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，葡萄糖水平升高促进了自由基的形成(p<；0.01)。成功地建立了ADTIQ检测方法，并对ADTIQ水平进行了检测和定量。在高血糖细胞模型和糖尿病大鼠模型中测定其前体MG和多巴胺(DA)的水平。并对糖代谢相关蛋白进行了检测。与对照组相比，无论是在高血糖细胞模型中，还是在糖尿病大鼠的脑内，ADTIQ和MG水平都显著升高(p<；0.01)。研究发现，糖酵解途径的七种关键酶在糖尿病大鼠的大脑中含量显著增加。此外，还发现糖尿病大鼠三磷酸腺苷合成酶和超氧化物歧化酶的表达水平明显低于对照组。因此，ADTIQ的表达水平在高血糖条件下被发现是升高的。这些结果表明，ADTIQ来源于MG，其水平在糖尿病时升高，可能是对多巴胺能神经元的神经毒素，最终导致帕金森病。
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.