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Differential Involvement of Intracellular Ca2+ in 1-Methyl-4-phenylpyridinium- or 6-Hydroxydopamine-Induced Cell Viability Loss in PC12 Cells

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Abstract

1-Methyl-4-phenylpyridinium (MPP+) or 6-hydroxydopamine (6-OHDA) caused a nuclear damage, the mitochondrial membrane permeability changes, leading to the cytochrome c release and caspase-3 activation, the formation of reactive oxygen species and the depletion of GSH in PC12 cells. Nicardipine (a calcium channel blocker), EGTA (an extracellular calcium chelator), BAPTA-AM (a cell permeable calcium chelator) and calmodulin antagonists (W-7 and calmidazolium) attenuated the MPP+-induced mitochondrial damage and cell death. In contrast, the compounds did not reduce the toxicity of 6-OHDA. Treatment with MPP+ or 6-OHDA evoked the elevation of intracellular Ca2+ levels. Unlike cell injury, addition of nicardipine, BAPTA-AM and calmodulin antagonists prevented the elevation of intracellular Ca2+ levels due to both toxins. The results show that the MPP+-induced formation of the mitochondrial permeability transition seems to be mediated by elevation of intracellular Ca2+ levels and calmodulin action. In contrast, the 6-OHDA-induced cell death seems to be mediated by Ca2+-independent manner.

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Acknowledgments

This work was supported by the Korea Research Foundation Grant (KRF-2004-015-E00093) to C.S. Lee.

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Authors and Affiliations

  1. Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, 156-756, South Korea

    Dong Hee Lee, Young Su Han, Eun Sook Han & Chung Soo Lee

  2. Department of Physiology, College of Medicine, Chung-Ang University, Seoul, 156-756, South Korea

    Hyoweon Bang

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Correspondence to Chung Soo Lee.

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Lee, D.H., Han, Y.S., Han, E.S. et al. Differential Involvement of Intracellular Ca2+ in 1-Methyl-4-phenylpyridinium- or 6-Hydroxydopamine-Induced Cell Viability Loss in PC12 Cells. Neurochem Res 31, 851–860 (2006). https://doi.org/10.1007/s11064-006-9088-9

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  • DOI: https://doi.org/10.1007/s11064-006-9088-9

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