title: Overexpression of torsinA in PC12 cells protects against toxicity.
abstract: Childhood-onset dystonia is an autosomal dominant movement disorder associated with a three base pair (GAG) deletion mutation in the DYT1 gene. This gene encodes a novel ATP-binding protein called torsinA, which in the central nervous system is expressed exclusively in neurons. Neither the function of torsinA nor its role in the pathophysiology of DYT1 dystonia is known. In order to better understand the cellular functions of torsinA, we established PC12 cell lines overexpressing wild-type or mutant torsinA and subjected them to various conditions deleterious to cell survival. Treatment of control PC12 cells with an inhibitor of proteasomal activity, an oxidizing agent, or trophic withdrawal, resulted in cell death, whereas PC12 cells that overexpressed torsinA were significantly protected against each of these treatments. Overexpression of mutant torsinA failed to protect cells against trophic withdrawal. These results suggest that torsinA may play a protective role in neurons against a variety of cellular insults.
authors.affiliation: Department of Neurology, Mount Sinai School of Medicine, New York 10029, USA. pullani.shashi@mssm.edu
authors.forename: P
authors.initials: P
authors.lastname: Shashidharan
authors.forename: Nicolae
authors.initials: N
authors.lastname: Paris
authors.forename: Daniela
authors.initials: D
authors.lastname: Sandu
authors.forename: Laina
authors.initials: L
authors.lastname: Karthikeyan
authors.forename: Kevin St P
authors.initials: KS
authors.lastname: McNaught
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Walker
authors.forename: C Warren
authors.initials: CW
authors.lastname: Olanow
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival; D016895:Culture Media, Serum-Free / Q000633:toxicity; D015853:Cysteine Proteinase Inhibitors / Q000633:toxicity; D015870:Gene Expression / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000633:toxicity; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling; D007976:Leupeptins / Q000633:toxicity; D018832:Molecular Chaperones; D016716:PC12 Cells; D051381:Rats; D017384:Sequence Deletion; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D016895:Culture Media, Serum-Free; D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D018832:Molecular Chaperones; C491549:Tor1a protein, rat; D006861:Hydrogen Peroxide; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde