title: 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.
abstract: 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.
authors.affiliation: Division of Chemical Metrology and Analytical Science, National Institute of Metrology, Beijing 100013, P.R. China.
authors.forename: De-Wei
authors.initials: DW
authors.lastname: Song
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, P.R. China.
authors.forename: Nian
authors.initials: N
authors.lastname: Xin
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, P.R. China.
authors.forename: Bing-Jie
authors.initials: BJ
authors.lastname: Xie
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, P.R. China.
authors.forename: Yu-Juan
authors.initials: YJ
authors.lastname: Li
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, P.R. China.
authors.forename: Ling-Yan
authors.initials: LY
authors.lastname: Meng
authors.affiliation: Division of Chemical Metrology and Analytical Science, National Institute of Metrology, Beijing 100013, P.R. China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Li
authors.affiliation: Marquette University, Milwaukee, WI 53233, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Schläppi
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, P.R. China.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Deng
mesh_terms: D000818:Animals; D048909:Diabetes Complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D006943:Hyperglycemia / Q000235:genetics / Q000473:pathology; D007546:Isoquinolines / Q000737:chemistry / Q000378:metabolism*; D009498:Neurotoxins / Q000737:chemistry / Q000378:metabolism*; D010300:Parkinson Disease / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D044005:Tetrahydroisoquinolines / Q000378:metabolism*
chemical_list: C573869:1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline; D007546:Isoquinolines; D009498:Neurotoxins; D044005:Tetrahydroisoquinolines; D017665:Hydroxyl Radical; C036617:salsolinol; D005947:Glucose