Abstract | BACKGROUND: METHODS: LC-MS/MS, 1H NMR and infrared spectroscopy identified the structure of ADTIQ. The Annexin V-FITC/PI, MTT and western blot analysis were used to measure the neurotoxicity of ADTIQ. The levels of ADTIQ and methylglyoxal were detected by LC-MS/MS. RESULTS: Here we report the chemical synthesis of ADTIQ, demonstrate its biosynthesis in SH-SY5Y neuroblastoma cell line and investigate its role in the pathogenesis of PD. In addition, a significant increase in the level of ADTIQ was detected in the brains of transgenic mice expressing mutant forms (A53T or A30P) of α- synuclein. ADTIQ also reduced the cell viability and induced mitochondrial apoptosis in dopaminergic cells, suggesting that ADTIQ acts as an endogenous neurotoxin and potentially involved in the pathogenesis of PD. Methylglyoxal, a major byproduct of glucose metabolism and abnormalities in glucose metabolism could influence the levels of ADTIQ. Consistent with the hypothesis, increased levels of ADTIQ and methylglyoxal were detected in the striatum of diabetic rats and SH-SY5Y cells cultured in the presence of high glucose concentrations. CONCLUSIONS: Increased levels of ADTIQ could be related with Hyperglycemia and death of dopaminergic neurons. GENERAL SIGNIFICANCE: The increased levels of ADTIQ could be a reason of dopamine neuron dysfunction in diabetes. Therefore, ADTIQ may play a key role in increasing the risk for PD in patients with diabetes.
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Authors | Bingjie Xie, Fankai Lin, Kaleem Ullah, Lei Peng, Wei Ding, Rongji Dai, Hong Qing, Yulin Deng |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 459
Issue 3
Pg. 361-6
(Apr 10 2015)
ISSN: 1090-2104 [Electronic] United States |
PMID | 25744031
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Inc. All rights reserved. |
Chemical References |
- 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline
- Mutant Proteins
- Neurotoxins
- Tetrahydroisoquinolines
- alpha-Synuclein
- Pyruvaldehyde
- Glucose
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Topics |
- Animals
- Brain
(drug effects, metabolism, pathology)
- Cell Death
(drug effects)
- Cell Line
- Diabetes Mellitus, Experimental
(metabolism)
- Dopaminergic Neurons
(drug effects, pathology)
- Glucose
(metabolism)
- Humans
- Hyperglycemia
(etiology, metabolism)
- Mice
- Mice, Transgenic
- Mutant Proteins
(genetics, metabolism)
- Neurotoxins
(chemistry, metabolism, toxicity)
- Parkinson Disease
(etiology, metabolism, pathology)
- Pyruvaldehyde
(metabolism)
- Rats
- Rats, Sprague-Dawley
- Tetrahydroisoquinolines
(chemistry, metabolism, toxicity)
- alpha-Synuclein
(genetics, metabolism)
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