{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T01:32:09Z","timestamp":1759541529240},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,9,24]],"date-time":"2009-09-24T00:00:00Z","timestamp":1253750400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2010,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Notechis scutatus scutatus<\/jats:italic> notexin induced apoptotic death of SK\u2010N\u2010SH cells accompanied with downregulation of Bcl\u2010xL, upregulation of Bak, mitochondrial depolarization, and ROS generation. Upon exposure to notexin, Ca<jats:sup>2+<\/jats:sup>\u2010mediated JNK and p38 MAPK activation were observed in SK\u2010N\u2010SH cells. Production of ROS was a downstream event followed by Ca<jats:sup>2+<\/jats:sup>\u2010mediated mitochondrial alteration. Notexin\u2010induced cell death, mitochondrial depolarization, and ROS generation were suppressed by SB202190 (p38 MAPK inhibitor) and SP600125 (JNK inhibitor). Moreover, phospho\u2010p38 MAPK and phospho\u2010JNK were proved to be involved in Bcl\u2010xL degradation, and overexpression of Bcl\u2010xL attenuated the cytotoxic effect of notexin. Bak upregulation was elicited by p38 MAPK\u2010mediated ATF\u20102 activation and JNK\u2010mediated c\u2010Jun activation. Suppression of Bak upregulation by ATF\u20102 siRNA or c\u2010Jun siRNA attenuated notexin\u2010evoked mitochondrial depolarization and rescued viability of notexin\u2010treated cells. Taken together, our data indicate that notexin\u2010induced apoptotic death of SK\u2010N\u2010SH cells is mediated through mitochondrial alteration triggering by Ca<jats:sup>2+<\/jats:sup>\u2010evoked p38 MAPK\/ATF\u20102 and JNK\/c\u2010Jun signaling pathways. J. Cell. Physiol. 222:177\u2013186, 2010. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.21934","type":"journal-article","created":{"date-parts":[[2009,9,24]],"date-time":"2009-09-24T17:47:53Z","timestamp":1253814473000},"page":"177-186","source":"Crossref","is-referenced-by-count":18,"title":["Calcium\u2010stimulated mitogen\u2010activated protein kinase activation elicits Bcl\u2010xL downregulation and Bak upregulation in notexin\u2010treated human neuroblastoma SK\u2010N\u2010SH cells"],"prefix":"10.1002","volume":"222","author":[{"given":"Ku\u2010Chung","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen\u2010Hsin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei\u2010Hsiu","family":"Kao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long\u2010Sen","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,9,24]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.5.1886-1896.2000"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1014"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00139.2004"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01886855"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2007.10.006"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3410233"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M511052200"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601126"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21886"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401950"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10863-006-9054-x"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2006.03.016"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5381.1309"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-005-0792-8"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0953-816x.2001.01699.x"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01589"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2008.01.002"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702344200"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5303.1132"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1022945107762"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20616"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2005.06.011"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401975"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1120640"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610176200"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M803243200"},{"key":"e_1_2_5_28_1","first-page":"155","volume-title":"Venom phospholipase A2 enzymes: Structure, function and mechanism","author":"Rosenberg P","year":"1997"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.02035.x"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(02)01477-6"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-0186(02)00118-3"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-003-0741-4"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M805019200"},{"key":"e_1_2_5_34_1","first-page":"2922","article-title":"The expanding role of mitochondria in apoptosis","volume":"15","author":"Wang X","year":"2001","journal-title":"Genes Dev"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(92)81238-H"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.21934","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.21934","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T14:40:54Z","timestamp":1697294454000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.21934"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,9,24]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,1]]}},"alternative-id":["10.1002\/jcp.21934"],"URL":"https:\/\/doi.org\/10.1002\/jcp.21934","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,9,24]]}}}