title: Concurrent calpain and caspase-3 mediated proteolysis of alpha II-spectrin and tau in rat brain after methamphetamine exposure: a similar profile to traumatic brain injury.
abstract: Neurotoxicity in rat cortex and hippocampus following acute methamphetamine administration was characterized and compared to changes following traumatic brain injury. Doses of 10, 20, and 40 mg/kg of methamphetamine produced significant increases in calpain- and caspase-cleaved alpha II-spectrin and tau protein fragments, suggesting cell injury or death. Changes in proteolytic products were significantly increased over vehicle controls. Use of fragment specific biomarkers detected prominent calpain-mediated protein fragments in the cortex and hippocampus while caspase-mediated protein fragments were also detected in the hippocampus. Remarkably, proteolytic product increases at the 40 mg/kg dose after 24 h were as high as those observed in experimental traumatic brain injury. Use of calpain and caspase proteolytic inhibitors may be useful in preventing methamphetamine-induced neurotoxicity.
authors.affiliation: University of Florida Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA. warren@ufl.edu
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Warren
authors.forename: Firas H
authors.initials: FH
authors.lastname: Kobeissy
authors.forename: Ming Cheng
authors.initials: MC
authors.lastname: Liu
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hayes
authors.forename: Mark S
authors.initials: MS
authors.lastname: Gold
authors.forename: Kevin K W
authors.initials: KK
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001930:Brain Injuries / Q000201:enzymology / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D008297:Male; D008694:Methamphetamine / Q000633:toxicity; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020258:Neurotoxicity Syndromes / Q000201:enzymology / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013049:Spectrin / Q000378:metabolism*; D016875:tau Proteins
chemical_list: C489131:Mapt protein, rat; D009419:Nerve Tissue Proteins; D016875:tau Proteins; D013049:Spectrin; D008694:Methamphetamine; D002154:Calpain; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases