研究论文

高糖诱导ADTIQ的生成和多巴胺的代谢失衡

  • 谢冰洁 ,
  • 武晗燕 ,
  • 邓玉林
展开
  • 北京理工大学生命学院, 北京100081
谢冰洁,博士研究生,研究方向为神经退行性疾病,电子信箱:xiebingjie19860128@126.com

收稿日期: 2015-07-02

  修回日期: 2015-07-31

  网络出版日期: 2015-09-12

基金资助

国家重大科学仪器设备开发专项(2012YQ040140)

Hyperglycemia induced generation of ADTIQ and dopamine metabolism imbalance

  • XIE Bingjie ,
  • WU Hanyan ,
  • DENG Yulin
Expand
  • School of Life Science, Beijing Institute of Technology, Beijing 100081, China

Received date: 2015-07-02

  Revised date: 2015-07-31

  Online published: 2015-09-12

摘要

2 型糖尿病患者比正常人更容易患帕金森病(PD),而新内源性神经毒素1-乙酰基-6, 7-二羟基-1, 2, 3,4-四氢异喹啉(ADTIQ)可能成为2 型糖尿病并发PD 的一个关键因素,ADTIQ 是由丙酮醛与多巴胺反应合成,但是其在多巴胺能神经元中的生成条件,以及在糖尿病情况下ADTIQ 的生成是否影响多巴胺代谢尚不清楚。本研究以SH-SY5Y 细胞为模型,研究ADTIQ 在细胞模型中的生成条件,发现ADTIQ 是在葡萄糖代谢旺盛的条件下,丙酮醛内源性产生与神经元内的多巴胺反应生成。研究揭示,高糖条件下,SH-SY5Y 细胞和2 型糖尿病的大鼠模型中外周多巴胺的质量浓度减少,而与多巴胺合成和转运相关的酪氨酸羟化酶和多巴胺转运体合成增加。可见,高糖能诱导SH-SY5Y 细胞内ADTIQ 的生成和多巴胺代谢的失衡,ADTIQ 的生成可能成为糖尿病并发PD 的关键因素。

本文引用格式

谢冰洁 , 武晗燕 , 邓玉林 . 高糖诱导ADTIQ的生成和多巴胺的代谢失衡[J]. 科技导报, 2015 , 33(17) : 90 -95 . DOI: 10.3981/j.issn.1000-7857.2015.17.010

Abstract

Recent studies show that for the type 2 diabetes the Parkinson's disease is more likely to be developed than for normal diabetes, and the 1-acetyl-6, 7-dihydroxyl-1, 2, 3, 4-tetrahydroisoquinoline (ADTIQ) could be a key factor associated with the diabetes and the PD. In the present study, the SH-SY5Y cells are used as a model to investigate the ADTIQ generated conditions. It is found that the hyperglycemia could induce the increase of the endogenous methylglyoxal, which might react with the dopamine to generate the ADTIQ. Again, the hyperglycemia leads to a reduction of the dopamine in the SH-SY5Y cells and the plasma of the type 2 diabetic rats, and an increase of the tyrosine hydroxylase (TH) and the dopamine transporter (DAT). So, the hyperglycemia induces the generation of the ADTIQ and the dopamine metabolism imbalance. The generation of the ADTIQ could play a key role in increasing the risk of the PD in patients with diabetes.

参考文献

1] Shastry B S. Parkinson disease:Etiology, pathogenesis and future of gene therapy[J]. Neuroscience Research, 2001, 41(1):5-12.
[2] Chase T N, Oh J D, Blanchet P J. Neostriatal mechanisms in parkinson's disease[J]. Neurology, 1998, 51(Suppl 2):S30-35.
[3] Hu G, Jousilahti P, Bidel S, et al. Type 2 diabetes and the risk of parkinson's disease[J]. Diabetes Care, 2007, 30(4):842-847.
[4] Driver J A, Smith A, Buring J E, et al. Prospective cohort study of type 2 diabetes and the risk of parkinson's disease[J]. Diabetes Care, 2008, 31 (10):2003-2005.
[5] Xu Q, Park Y, Huang X, et al. Diabetes and risk of parkinson's disease[J]. Diabetes Care, 2011, 34(4):910-915.
[6] Cereda E, Barichella M, Pedrolli C, et al. Diabetes and risk of parkinson's disease[J]. Movement Disorders, 2013, 28(2):257.
[7] Cereda E, Barichella M, Pedrolli C, et al. Diabetes and risk of parkinson's disease:A systematic review and meta-analysis[J]. Diabetes Care, 2011, 34(12):2614-2623.
[8] Choi J Y, Jang E H, Park C S, et al. Enhanced susceptibility to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine neurotoxicity in high-fat dietinduced obesity[J]. Free Radical Biology and Medicine, 2005, 38(6):806-816.
[9] Morris J K, Bomhoff G L, Stanford J A, et al. Neurodegeneration in an animal model of parkinson's disease is exacerbated by a high-fat diet[J]. American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2010, 299(4):1082-1090.
[10] Santiago J A, Potashkin J A. Sha red dysregulated pathways lead to parkinson's disease and diabetes[J]. Trends in Molecular Medicine, 2013, 19(3):176-186.
[11] Palacios N, Ascherio A. Reply to:Diabetes and risk of parkinson's disease[J]. Movement Disorders, 2013, 28(2):258.
[12] Deng Y, Zhang Y, Li Y, et al. Occurrence and distribution of salsolinollike compound, 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (adtiq) in parkinsonian brains[J]. Journal of Neural Transmission, 2012, 119(4):435-441.
[13] Xie B, Lin F, Ullah K, et al. A newly discovered neurotoxin adtiq associated with hyperglycemia and parkinson's disease[J]. Biochemical and Biophysical Research Communications, 2015, 459(3):361-366.
[14] Kikuchi S, Shinpo K, Moriwaka F, et al. Neurotoxicity of methylglyoxal and 3-deoxyglucosone on cultured cortical neurons:Synergism between glycation and oxidative stress, possibly involved in neurodegenerative diseases[J]. Journal of Neuroscience Research, 1999, 57(2):280-289.
[15] Shinpo K, Kikuchi S, Sasaki H, et al. Selective vulnerability of spinal motor neurons to reactive dicarbonyl compounds, intermediate products of glycation, in vitro:Implication of inefficient glutathione system in spinal motor neurons[J]. Brain Research, 2000, 861(1):151-159.
[16] Lu J, Randell E, Han Y, et al. Increased plasma methylglyoxal level, inflammation, and vascular endothelial dysfunction in diabetic nephropathy[J]. Clinical Biochemistry, 2011, 44(4):307-311.
[17] Vander D L. Methylglyoxal, diabetes mellitus and diabetic complications[J]. Drug Metabolism and Drug Interactions, 2008, 23(1/2):93-124.
[18] Turk Z, Nemet I, Varga L, et al. Elevated level of methylglyoxal during diabetic ketoacidosis and its recovery phase[J]. Diabetes & Metabolism, 2006, 32(2):176-180.
[19] Hipkiss A R. Aging risk factors and parkinson's disease:Contrasting roles of common dietary constituents[J]. Neurobiology of Aging, 2014, 35 (6):1469-1472.
[20] Alan R. Parkinson's disease and type-2 diabetes:Methylglyoxal may be a common causal agent; carnosine could be protective[J/OL]. Molecular Medicine & Therapeutics[2015-07-02]. http://mattitolonen.fi/files/pdf/Hipkiss_2013.pdf.
[21] Burke W J, Li S W, Chung H D, et al. Neurotoxicity of mao metabolites of catecholamine neurotransmitters:Role in neurodegenerative diseases[J]. Neurotoxicology, 2004, 25(1/2):101-115.
[22] Stokes A H, Hastings T G, Vrana K E. Cytotoxic and genotoxic potential of dopamine[J]. Journal of Neuroscience Research, 1999, 55(6):659-665.
[23] Kitayama S, Wang J B, Uhl G R. Dopamine transporter mutants selectively enhance mpp+ transport[J]. Synapse, 1993, 15(1):58-62.
[24] Boada J, Cutillas B, Roig T, et al. Mpp(+)-induced mitochondrial dysfunction is potentiated by dopamine[J]. Biochemical and Biophysical Research Communications, 2000, 268(3):916-920.
[25] Song D W, Xin N, Xie B J, et al. Formation of a salsolinol-like compound, theneurotoxin,1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, in a cellular model of hyperglycemia and a rat model of diabetes[J]. International Journal of Molecular Medicine, 2014, 33(3):736-742.
[26] Morris J K, Bomhoff G L, Gorres B K, et al. Insulin resistance impairs nigrostriatal dopamine function[J]. Experimental Neurology, 2011, 231 (1):171-180.
[27] Schultz W. Getting formal with dopamine and reward[J]. Neuron, 2002, 36(2):241-263.
[28] Xie B, Lin F, Peng L, et al. Methylglyoxal increased dopamine level and led to oxidative stress in sh-sy5y cells[J]. Acta Biochimica et Biophysica Sinica, 2014, 46(11):950-956.
文章导航

/