Divergent role of calcium on Abeta- and MPTP-induced cell death in SK-N-SH neuroblastoma |
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Authors: | Lee Wan-Shin Tsai Wei-Jen Yeh Pen-Ho Wei Bai-Luh Chiou Wen-Fei |
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Affiliation: | Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC. |
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Abstract: | We attempted to clarify the role of Ca2+ in cell death caused by beta-amyloid protein (Abeta) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in SK-N-SH neuroblastoma, respectively. Two insults both reduced cell viability in a concentration-dependent manner and induced equal cytotoxicity in the presence of 20 microM Abeta and 0.4 mM MPTP for 72 h, respectively (68+/-7 vs. 64+/-6% viability). Time-related study showed that Abeta evoked cell death occurred quickly at 24 h. Relatively, MPTP exhibited a delayed cell death significantly after 72 h of culture. Pretreating the cells with nimodipine and chelating of Ca2+ by EGTA plus 1,2-bis-(O-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM) successfully rescued Abeta-induced cell death but failed to prevent MPTP toxicity. ELISA determination of mono/oligonucleosomes accumulation showed the mode of cell death evoked by MPTP was presumably apoptosis while by Abeta was necrosis. SK-N-SH cells constitutively expressed the alpha(1C) subunit of L-type Ca2+ channel and exposure to Abeta or MPTP for 96 h did not further modify its expression. By contrast, alpha(1D) subunit was undetectable or low level expressed in basal condition, but was induced to express after Abeta and MPTP stimulation in a time-dependent manner. Functional assay revealed that KCl-evoked [Ca2+]i rise was significantly greater in Abeta-, but not in MPTP-treated cells when compared with control. Taken together, these results showed that Abeta and MPTP elicited different mode of cell death in SK-N-SH. Nevertheless, Ca2+ overload seems to solely display a crucial role in Abeta-induced cytotoxicity and over-expressed alpha(1D) may contribute to the disruption of cellular Ca2+ homeostasis. |
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Keywords: | β-amyloid protein (Aβ) 1-Methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) Necrosis Apoptosis Ca2+ homeostasis SK-N-SH neuroblastoma |
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