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

Dong Jae Jun, Jaeyoon Kim, Sang Yong Jung, Ran Song, Ji Hyun Noh, Yong Soo Park, Sung Ho Ryu, Joung Hun Kim, Young Yun Kong, Jun Mo Chung, Kyong Tai Kim

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

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.

Original languageEnglish
Pages (from-to)37350-37358
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number52
DOIs
StatePublished - 28 Dec 2007

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