Differential effects of methyl-4-phenylpyridinium ion,rotenone,and Paraquat on differentiated SH-SY5Y cells

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 nnitro-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. © 2013 joão barbosa martins et al.