title: Methylglyoxal increases dopamine level and leads to oxidative stress in SH-SY5Y cells.
abstract: More and more studies have suggested that methylglyoxal (MGO) induced by type-2 diabetes is related to Parkinson's disease (PD). However, little is known about the molecular mechanism. In this study, we explored the MGO toxicity in neuroblastoma SH-SY5Y cells. Neurotoxicity of MGO was measured by mitochondrial membrane potential, malondialdehyde, and methylthiazoletetrazolium assays. The levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and 1-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline (salsolinol) were detected by liquid chromatography-mass spectrometry/mass spectrometry. The expressions of tyrosine hydroxylase (TH) and dopamine transporter (DAT) were detected by reverse transcriptase polymerase chain reaction and western blot analysis. The results showed that MGO induced an increase in TH and DAT expressions in SH-SY5Y neuroblastoma cells, while the levels of dopamine, DOPAC, and endogenous neurotoxin salsolinol also increased. Aminoguanidine (AG) is an inhibitor of MGO. It was found that AG could decrease the reactive oxygen species (ROS) level induced by MGO, but could not inhibit an increase of TH, DAT and dopamine. The increase of dopamine, DOPAC and salsolinol levels could lead to high ROS and mitochondrial damage. This study suggests that ROS caused by dopamine could contribute to the damage of dopaminergic neurons when MGO is increased during the course of diabetes.
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, China.
authors.forename: Bingjie
authors.initials: B
authors.lastname: Xie
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, China.
authors.forename: Fankai
authors.initials: F
authors.lastname: Lin
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Peng
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, China.
authors.forename: Kaleem
authors.initials: K
authors.lastname: Ullah
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, China.
authors.forename: Hanyan
authors.initials: H
authors.lastname: Wu
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Qing
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, China deng@bit.edu.cn.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Deng
mesh_terms: D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000633:toxicity; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008959:Models, Neurological; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D010300:Parkinson Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D011765:Pyruvaldehyde / Q000037:antagonists & inhibitors / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D006146:Guanidines; D007546:Isoquinolines; D009498:Neurotoxins; D012333:RNA, Messenger; D011765:Pyruvaldehyde; C036617:salsolinol; D014446:Tyrosine 3-Monooxygenase; C004479:pimagedine; D004298:Dopamine
keywords: Parkinson's disease; dopamine; dopamine transporter; methylglyoxal; tyrosine hydroxylase