Differential Effects of Methyl-4-Phenylpyridinium Ion, Rotenone, and Paraquat on Differentiated SH-SY5Y Cells
Joint Authors
Capela, João Paulo
Carvalho, Félix
Martins, João Barbosa
Bastos, Maria de Lourdes
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-03-20
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Pharmacy, Health & Medical Sciences
Medicine
Abstract EN
Paraquat (PQ), a cationic nonselective bipyridyl herbicide, has been used as neurotoxicant to modulate Parkinson’s disease in laboratory settings.
Other compounds like rotenone (ROT), a pesticide, and 1-methyl-4-phenylpyridinium ion (MPP+) have been widely used as neurotoxicants.
We compared the toxicity of these three neurotoxicants using differentiated dopaminergic SH-SY5Y human cells, aiming to elucidate their differential effects.
PQ-induced neurotoxicity was shown to be concentration and time dependent, being mitochondrial dysfunction followed by neuronal death.
On the other hand, cells exposure to MPP+ induced mitochondrial dysfunction, but not cellular lyses.
Meanwhile, ROT promoted both mitochondrial dysfunction and neuronal death, revealing a biphasic pattern.
To further elucidate PQ neurotoxic mechanism, several protective agents were used.
SH-SY5Y cells pretreatment with tiron (TIR) and 2-hydroxybenzoic acid sodium salt (NaSAL), both antioxidants, and Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), a nitric oxide synthase inhibitor, partially protected against PQ-induced cell injury.
Additionally, 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenyl-propyl)piperazine (GBR 12909), a dopamine transporter inhibitor, and cycloheximide (CHX), a protein synthesis inhibitor, also partially protected against PQ-induced cell injury.
In conclusion, we demonstrated that PQ, MPP+, and ROT exerted differential toxic effects on dopaminergic cells.
PQ neurotoxicity occurred through exacerbated oxidative stress, with involvement of uptake through the dopamine transporter and protein synthesis.
American Psychological Association (APA)
Martins, João Barbosa& Bastos, Maria de Lourdes& Carvalho, Félix& Capela, João Paulo. 2013. Differential Effects of Methyl-4-Phenylpyridinium Ion, Rotenone, and Paraquat on Differentiated SH-SY5Y Cells. Journal of Toxicology،Vol. 2013, no. 2013, pp.1-10.
https://search.emarefa.net/detail/BIM-464636
Modern Language Association (MLA)
Martins, João Barbosa…[et al.]. Differential Effects of Methyl-4-Phenylpyridinium Ion, Rotenone, and Paraquat on Differentiated SH-SY5Y Cells. Journal of Toxicology No. 2013 (2013), pp.1-10.
https://search.emarefa.net/detail/BIM-464636
American Medical Association (AMA)
Martins, João Barbosa& Bastos, Maria de Lourdes& Carvalho, Félix& Capela, João Paulo. Differential Effects of Methyl-4-Phenylpyridinium Ion, Rotenone, and Paraquat on Differentiated SH-SY5Y Cells. Journal of Toxicology. 2013. Vol. 2013, no. 2013, pp.1-10.
https://search.emarefa.net/detail/BIM-464636
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-464636