title: Extracellular ATP mediates necrotic cell swelling in SN4741 dopaminergic neurons through P2X7 receptors.
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 P2X(7) receptors (P2X(7)Rs) are abundantly expressed in SN4741 cells, and both ATP-induced swelling and cell death are reversed by pretreatment with the P2X(7)Rs antagonist, KN62, or by knock-down of P2X(7)Rs with small interfering RNAs. Therefore, extracellular ATP release from injured tissues may act as an accelerating factor in necrotic SN4741 dopaminergic cell death via P2X(7)Rs.
authors.affiliation: Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, Nam-Gu, Pohang, Republic of Korea.
authors.forename: Dong-Jae
authors.initials: DJ
authors.lastname: Jun
authors.forename: Jaeyoon
authors.initials: J
authors.lastname: Kim
authors.forename: Sang-Yong
authors.initials: SY
authors.lastname: Jung
authors.forename: Ran
authors.initials: R
authors.lastname: Song
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Noh
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Park
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Ryu
authors.forename: Joung-Hun
authors.initials: JH
authors.lastname: Kim
authors.forename: Young-Yun
authors.initials: YY
authors.lastname: Kong
authors.forename: Jun-Mo
authors.initials: JM
authors.lastname: Chung
authors.forename: Kyong-Tai
authors.initials: KT
authors.lastname: Kim
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008822:Mice, Transgenic; D009336:Necrosis; D009474:Neurons / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7; D013997:Time Factors
chemical_list: C546469:P2rx7 protein, mouse; D034741:RNA, Small Interfering; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000255:Adenosine Triphosphate; D053148:Caspase 3; D004298:Dopamine