Calpastatin reduces methamphetamine-induced induction in c-Jun phosphorylation, Bax and cell death in neuroblastoma SH-SY5Y cells.
Methamphetamine (METH) is one of the most commonly abused substances in today's society. Many studies have shown that the process of cell death induced by METH involves with the reception of death signals, an increase in pro-apoptotic proteins (Bax) and an activation of cysteine protease death pathway. The objective of this study was to investigate the neuroprotective effects of calpastatin against METH-induced toxicity in SH-SY5Y neuroblastoma cells by observing cell viability, phosphorylation of transcription factor, c-Jun (phospho-c-Jun) and levels of Bax and Bcl-2. The results showed that METH significantly decreased cell viability in SH-SY5Y cultured cells. Conversely, increase in phospho-c-Jun and Bax/Bcl-2 ratio was observed in METH-treated cells. Calpastatin reversed the toxic effect of METH by increasing cell viability, reducing phospho-c-Jun and Bax/Bcl-2 ratio in METH-treated cells. These results indicated that calpastatin has the capacity to reverse an activation of the death process in METH-treated dopaminergic cell lines.
Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Jirapa
J
Chetsawang
Wilasinee
W
Suwanjang
Nipawan
N
Pirompul
Piyarat
P
Govitrapong
Banthit
B
Chetsawang
D000704:Analysis of Variance; D000818:Animals; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D008694:Methamphetamine / Q000494:pharmacology*; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D051381:Rats; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D000697:Central Nervous System Stimulants; D015853:Cysteine Proteinase Inhibitors; D016755:Proto-Oncogene Proteins c-jun; D051028:bcl-2-Associated X Protein; D008694:Methamphetamine; C033668:calpastatin