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Extracellular ATP mediates necrotic cell swelling in SN4741 dopaminergic neurons through P2X7 receptors

Title
Extracellular ATP mediates necrotic cell swelling in SN4741 dopaminergic neurons through P2X7 receptors
Authors
Jun D.-J.Kim J.Jung S.-Y.Song R.Noh J.-H.Park Y.-S.Ryu S.-H.Kim J.-H.Kong Y.-Y.Chung J.-M.Kim K.-T.
Ewha Authors
정준모
SCOPUS Author ID
정준모scopus
Issue Date
2007
Journal Title
Journal of Biological Chemistry
ISSN
0021-9258JCR Link
Citation
vol. 282, no. 52, pp. 37350 - 37358
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Extracellular ATP has recently been identified as an important regulator of cell death in response to pathological insults. When SN4741 cells, which are dopaminergic neurons derived from the substantia nigra of transgenic mouse embryos, are exposed to ATP, cell death occurs. This cell death is associated with prominent cell swelling, loss of ER integrity, the formation of many large cytoplasmic vacuoles, and subsequent cytolysis and DNA release. In addition, the cleavage of caspase-3, a hallmark of apoptosis, is induced by ATP treatment. However, caspase inhibitors do not overcome ATP-induced cell death, indicating that both necrosis and apoptosis are associated with ATP-induced cell death and suggesting that a necrotic event might override the apoptotic process. In this study we also found that P2X7 receptors (P2X7Rs) are abundantly expressed in SN4741 cells, and both ATP-induced swelling and cell death are reversed by pretreatment with the P2X7Rs antagonist, KN62, or by knock-down of P2X7Rs with small interfering RNAs. Therefore, extracellular ATP release from injured tissues may act as an accelerating factor in necrotic SN4741 dopaminergic cell death via P2X7Rs. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.
DOI
10.1074/jbc.M707915200
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자연과학대학 > 생명과학전공 > Journal papers
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