title: Zinc protects SK-N-SH cells from methamphetamine-induced alpha-synuclein expression.
abstract: Methamphetamine (METH) is a well-known drug of abuse and neurotoxin that may cause temporary or permanent disturbances in the dopaminergic systems of the brain, predisposing individuals to Parkinsonism. Previously, we have shown that METH causes dopaminergic cell death by increasing the production of reactive oxygen species (ROS) and by depleting cellular ATP levels. These effects were abolished by pretreatment with ZnCl(2) which enhanced expression of the zinc binding protein, metallothionein. In the present study, the effects of ZnCl(2) on alpha-synuclein expression were examined further in METH-treated SK-N-SH cells in culture. We show that METH significantly increased alpha-synuclein expression in a dose-dependent manner after inducing oxidative stress. Pretreatment with ZnCl(2) (50microM) reversed this stimulatory effect. We propose that zinc mediates this neuroprotective response via the production of metallothionein.
authors.affiliation: Neuro-Behavioural Biology Center, Institute of Science and Technology for Research and Development, Mahidol University, Salaya, Nakornpathom 73170, Thailand.
authors.forename: Amornpan
authors.initials: A
authors.lastname: Ajjimaporn
authors.forename: Pansiri
authors.initials: P
authors.lastname: Phansuwan-Pujito
authors.forename: Manuchair
authors.initials: M
authors.lastname: Ebadi
authors.forename: Piyarat
authors.initials: P
authors.lastname: Govitrapong
mesh_terms: D045744:Cell Line, Tumor; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008694:Methamphetamine / Q000494:pharmacology*; D009447:Neuroblastoma; D015032:Zinc / Q000494:pharmacology*; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D015259:Dopamine Agents; D051844:alpha-Synuclein; D008694:Methamphetamine; D015032:Zinc