title: Calpain inhibition prevents ethanol-induced alterations in spinal motoneurons.
abstract: Long-term exposure of ethanol (EtOH) alters the structure and function in brain and spinal cord. The present study addresses the mechanisms of EtOH-induced damaging effects on spinal motoneurons in vitro. Altered morphology and biochemical changes of such damage were demonstrated by in situ Wright staining and DNA ladder assay. EtOH at low to moderate (25-50 mM) concentrations induced damaging effects in the motoneuronal scaffold which involved activation of proteases like μ-calpain and caspase-3. Caspase-8 was seen only at higher (100 mM) EtOH concentration. Further, pretreatment with calpeptin, a potent calpain inhibitor, confirmed the involvement of active proteases in EtOH-induced damage to motoneurons. The lysosomal enzyme cathepsin D was also elevated in the motoneurons by EtOH, and this effect was significantly attenuated by inhibitor treatment. Overall, EtOH exposure rendered spinal motoneurons vulnerable to damage, and calpeptin provided protection, suggesting a critical role of calpain activation in EtOH-induced alterations in spinal motoneurons.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 309 CSB, MSC 606, Charleston, SC, 29425, USA. samanta@musc.edu
authors.forename: Supriti
authors.initials: S
authors.lastname: Samantaray
authors.forename: Kaushal S
authors.initials: KS
authors.lastname: Patel
authors.forename: Varduhi H
authors.initials: VH
authors.lastname: Knaryan
authors.forename: Nakul P
authors.initials: NP
authors.lastname: Thakore
authors.forename: Stacy
authors.initials: S
authors.lastname: Roudabush
authors.forename: Jenna H
authors.initials: JH
authors.lastname: Heissenbuttle
authors.forename: Howard C
authors.initials: HC
authors.lastname: Becker
authors.forename: Naren L
authors.initials: NL
authors.lastname: Banik
mesh_terms: D015153:Blotting, Western; D002154:Calpain / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D004247:DNA / Q000187:drug effects; D004789:Enzyme Activation; D000431:Ethanol / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D009046:Motor Neurons / Q000187:drug effects*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects*
chemical_list: D000431:Ethanol; D004247:DNA; D002154:Calpain