Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Methylglyoxal increases dopamine level and leads to oxidative stress in SH-SY5Y cells. 2527 29

Despite extensive efforts to study the inflammatory process in the central nervous system of Parkinson's disease (PD) patients, little is known about the role of peripheral blood mononuclear cells (PBMCs) in PD. In the present study, we used an in vitro co-culture system to study the role of the human monocyte cell line THP-1 in medium conditioned by the neuroblastoma cell line SH-SY5Y damaged with the endogenous neurotoxin 1-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline (Salsolinol, Sal) in co-culture with the human glioma cell line U87. For this purpose, SH-SY5Y and U87 co-cultures were treated with Sal, and this conditioned medium containing mediators, including the potential effector CCL2, was isolated and applied to THP-1 cells. This treatment resulted in approximately 19 % cell proliferation as well as activation of mTOR and induction of phosphorylated 4E-BP1, S6K1, PI3K, and AKT proteins. Treatment with rapamycin, an mTOR inhibitor, attenuated the proliferation of THP-1 cells. U87 glial cells were essential for this as medium conditioned without them had no effect on THP-1 cells. These results suggest a positive effect of THP-1 cells on Sal-induced neurotoxicity in a cellular model of PD and this is likely mediated by the enhancement of cell proliferation through activation of the mTOR signaling pathway. Hence, PBMCs and their mTOR signaling pathway could be of therapeutic benefit in treating the endogenous neurotoxin-induced neuroinflammation in PD.
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PMID:Salsolinol Damaged Neuroblastoma SH-SY5Y Cells Induce Proliferation of Human Monocyte THP-1 Cells Through the mTOR Pathway in a Co-culture System. 2577 62


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