{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T18:03:52Z","timestamp":1783447432487,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,6,14]],"date-time":"2013-06-14T00:00:00Z","timestamp":1371168000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The P2X7 receptor\/channel responds to extracellular ATP and is associated with neuronal death and neuroinflammation in spinal cord injury and amyotrophic lateral sclerosis. Whether activation of P2X7 directly causes motor neuron death is unknown. We found that cultured motor neurons isolated from embryonic rat spinal cord express P2X7 and underwent caspase\u2010dependent apoptosis when exposed to exceptionally low concentrations of the P2X7 agonist 2\u2032(3\u2032)\u2010<jats:italic>O<\/jats:italic>\u2010(4\u2010Benzoylbenzoyl)\u2010ATP. The P2X7 inhibitors BBG, <jats:styled-content style=\"fixed-case\">oATP,<\/jats:styled-content> and KN\u201062 prevented 2\u2032(3\u2032)\u2010<jats:italic>O<\/jats:italic>\u2010(4\u2010Benzoylbenzoyl)\u2010ATP\u2010induced motor neuron death. The endogenous P2X7 agonist ATP induced motor neuron death at low concentrations (1\u2010100\u00a0\u03bcM). High concentrations of ATP (1\u00a0mM) paradoxically became protective due to degradation in the culture media to produce adenosine and activate adenosine receptors. P2X7\u2010induced motor neuron death was dependent on neuronal nitric oxide synthase\u2010mediated production of peroxynitrite, p38 activation, and autocrine FAS signaling. Taken together, our results indicate that motor neurons are highly sensitive to P2X7 activation, which triggers apoptosis by activation of the well\u2010established peroxynitrite\/FAS death pathway in motor neurons.<\/jats:p>","DOI":"10.1111\/jnc.12286","type":"journal-article","created":{"date-parts":[[2013,5,4]],"date-time":"2013-05-04T16:58:11Z","timestamp":1367686691000},"page":"382-388","source":"Crossref","is-referenced-by-count":51,"title":["P2X7 receptor\u2010induced death of motor neurons by a peroxynitrite\/<scp>FAS<\/scp>\u2010dependent pathway"],"prefix":"10.1111","volume":"126","author":[{"given":"Mandi","family":"Gandelman","sequence":"first","affiliation":[{"name":"Neurodegeneration Laboratory Institut Pasteur Montevideo Uruguay"},{"name":"Linus Pauling Institute Oregon State University Corvallis Qregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Levy","sequence":"additional","affiliation":[{"name":"Linus Pauling Institute Oregon State University Corvallis Qregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Cassina","sequence":"additional","affiliation":[{"name":"Departamento de Histolog\u00eda Facultad de Medicina Universidad de la Rep\u00fablica Montevideo Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Barbeito","sequence":"additional","affiliation":[{"name":"Neurodegeneration Laboratory Institut Pasteur Montevideo Uruguay"},{"name":"Instituto de Investigaciones Biol\u00f3gicas Clemente Estable Montevideo Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph S.","family":"Beckman","sequence":"additional","affiliation":[{"name":"Departamento de Histolog\u00eda Facultad de Medicina Universidad de la Rep\u00fablica Montevideo Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,6,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24159"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2008.06796.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2605"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21527"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2005.08.020"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901212"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1007"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-122275"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00233.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)63214-8"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5449.2498"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1215177110"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-7-33"},{"key":"e_1_2_7_15_1","first-page":"73","article-title":"Selective adenosine A(2a) receptor agonists reduce the apoptosis in an experimental model of spinal cord trauma","volume":"24","author":"Genovese T.","year":"2010","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb15078.x"},{"key":"e_1_2_7_17_1","volume-title":"Purification and culture of embryonic motor neurons: Neural cell culture: a practical approach","author":"Henderson C. E.","year":"1995"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0351168"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1983"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707915200"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1358\/dnp.2005.18.2.886479"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21152"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0911-05.2005"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-18-06879.2000"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0579-07.2007"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2005.05.014"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1159\/000089619"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2006.08.010"},{"key":"e_1_2_7_29_1","doi-asserted-by":"crossref","first-page":"7777","DOI":"10.1523\/JNEUROSCI.0823-07.2007","article-title":"Mitochondrial superoxide production and nuclear factor erythroid 2\u2010related factor 2 activation in p75 neurotrophin receptor\u2010induced motor neuron apoptosis","volume":"27","author":"Pehar M.","year":"2007","journal-title":"J. Neurosci."},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0902531106"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(93)90054-O"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0709684105"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.147.5.1049"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00905-4"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508774103"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2003.10.011"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0b013e3283179333"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.118901"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)00290-X"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1999.1491"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.274407"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2006.03.007"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-24-08526.2003"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1082"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705267104"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01639.x"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2377-6-12"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjnc.12286","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjnc.12286","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.12286","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T09:20:17Z","timestamp":1696238417000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.12286"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6,14]]},"references-count":46,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013,8]]}},"alternative-id":["10.1111\/jnc.12286"],"URL":"https:\/\/doi.org\/10.1111\/jnc.12286","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,6,14]]}}}