Calpastatin reduces calpain and caspase activation in methamphetamine-induced toxicity in human neuroblastoma SH-SY5Y cultured cells.
Methamphetamine (METH) is an abused psychostimulant drug that can cause neurotoxicity to dopaminergic cells. It has been demonstrated that METH can induce caspase- and calpain-dependent death cascades. The purpose of the present study was to investigate the functional role of calpastatin, a specific endogenous calpain inhibitor protein, on caspase and calpain activation in METH-induced degeneration in neuroblastoma SH-SY5Y cell cultures. In this study, we found that METH significantly decreased cell viability, tyrosine hydroxylase phosphorylation and calpastatin levels. Supplementation of cells with exogenous calpastatin was able to reverse the toxic effect of METH on reduction in cell viability and tyrosine hydroxylase phosphorylation. METH also significantly increased calpain levels, the formation of calpain-specific breakdown products and cleaved caspase-3 levels; once again, these effects were diminished by pretreating the cells with calpastatin. These data suggest the contribution of calpastatin as a potential regulatory factor for calpain- and caspase-dependent death processes.
Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhonpathom 73170, Thailand.
Wilasinee
W
Suwanjang
Pansiri
P
Phansuwan-Pujito
Piyarat
P
Govitrapong
Banthit
B
Chetsawang
D002135:Calcium-Binding Proteins / Q000494:pharmacology / Q000502:physiology*; D002154:Calpain / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D004789:Enzyme Activation; D006801:Humans; D008694:Methamphetamine / Q000633:toxicity*; D009447:Neuroblastoma; D018696:Neuroprotective Agents / Q000494:pharmacology; D010766:Phosphorylation; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002135:Calcium-Binding Proteins; D000697:Central Nervous System Stimulants; D018696:Neuroprotective Agents; D008694:Methamphetamine; C033668:calpastatin; D014446:Tyrosine 3-Monooxygenase; D002154:Calpain; D053148:Caspase 3; D020169:Caspases