Zinc rescues dopaminergic SK-N-SH cell lines from methamphetamine-induced toxicity.
Methamphetamine (METH) is a potent inducer of dopamine (DA) release, and is toxic to DA neurons. It has been reported that the formation of free radicals is an early signaling event that mediates cell death caused by METH. Currently, studies suggest that the generation of free radicals by oxidative catabolism of DA and dysfunction of the mitochondrial respiration chain are important mediators of neuronal death in Parkinson's disease (PD) and one process may counter the effect of the other. In our previous study, we investigated the deleterious effects of METH-induced reactive oxygen species (ROS) and mitochondrial dysfunction in dopaminergic SK-N-SH cells in culture, and assessed whether zinc-metallothionein induction provided mitochondrial protection against METH-induced mitochondrial dysfunction. Our present data demonstrate that METH enhances lipid peroxidation and mitochondrial manganese superoxide dismutase (MnSOD) enzyme levels, and decreases the antioxidant-reduced glutathione (GSH) together with an inhibition of mitochondrial complex-I activity. Pre-treatment with zinc markedly prevents the increase of lipid peroxidation and provides mitochondrial protection by scavenging free radicals via metallothionein and by increasing mitochondrial GSH and complex-I levels, thus rescuing SK-N-SH cells from METH toxicity. It should be emphasized that, however, it is still not clear that effects of METH on cultured SK-N-SH reliably model the effects of METH in the intact animal. Further studies in the intact animal are needed.
Neuro-Behavioral Biology Center, Institute of Science and Technology for Research and Development, Mahidol University, Salaya, Nakornpathom, Thailand. g4036011@hotmail.com
Amornpan
A
Ajjimaporn
Shaik
S
Shavali
Manuchair
M
Ebadi
Piyarat
P
Govitrapong
D000704:Analysis of Variance; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004298:Dopamine / Q000378:metabolism; D042967:Electron Transport Complex I / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008694:Methamphetamine / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D017967:Zinc Compounds / Q000494:pharmacology*
D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D017967:Zinc Compounds; D008694:Methamphetamine; D013482:Superoxide Dismutase; D042967:Electron Transport Complex I; D005978:Glutathione; D004298:Dopamine