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.
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.
Warren
Matthew W
MW
University of Florida Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA. warren@ufl.edu
Kobeissy
Firas H
FH
Liu
Ming Cheng
MC
Hayes
Ronald L
RL
Gold
Mark S
MS
Wang
Kevin K W
KK
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
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