{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:35:24Z","timestamp":1791279324533,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,11,19]],"date-time":"2009-11-19T00:00:00Z","timestamp":1258588800000},"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":[[2010,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Arachidonic acid (AA)\u2010induced apoptotic death of K562 cells (human chronic myeloid leukemic cells) was characteristic of reactive oxygen species (ROS) generation and mitochondrial depolarization. <jats:italic>N<\/jats:italic>\u2010Acetylcysteine pretreatment rescued viability of AA\u2010treated cells and abolished mitochondrial depolarization. In contrast to no significant changes in phospho\u2010JNK and phospho\u2010ERK levels, AA evoked notable activation of p38 MAPK. Unlike that of JNK and p38 MAPK, ERK suppression further reduced the viability of AA\u2010treated cells. Increases in Fas\/FasL protein expression, caspase\u20108 activation, the production of tBid and the loss of mitochondrial membrane potential were noted with K562 cells that were treated with a combination of U0126 and AA. Down\u2010regulation of FADD attenuated U0126\u2010evoked degradation of procaspase\u20108 and Bid. Abolition of p38 MAPK activation abrogated U0126\u2010elicited Fas\/FasL up\u2010regulation in AA\u2010treated cells. U0126 pretreatment suppressed c\u2010Fos phosphorylation but increased p38 MAPK\u2010mediated c\u2010Jun phosphorylation. Knock\u2010down of c\u2010Fos and c\u2010Jun protein expression by siRNA suggested that c\u2010Fos counteracted the effect of c\u2010Jun on Fas\/FasL up\u2010regulation. Taken together, our data indicate that AA induces the ROS\/mitochondria\u2010dependent death pathway and blocks the ERK pathway which enhances the cytotoxicity of AA through additionally evoking an autocrine Fas\u2010mediated apoptotic mechanism in K562 cells. J. Cell. Physiol. 222: 625\u2013634, 2010. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.21979","type":"journal-article","created":{"date-parts":[[2009,11,19]],"date-time":"2009-11-19T18:55:46Z","timestamp":1258656946000},"page":"625-634","source":"Crossref","is-referenced-by-count":8,"title":["Suppression of ERK signaling evokes autocrine Fas\u2010mediated death in arachidonic acid\u2010treated human chronic myeloid leukemia K562 cells"],"prefix":"10.1002","volume":"222","author":[{"given":"Ku\u2010Chung","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Hsin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long\u2010Sen","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,11,19]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2003.tb00203.x"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2004.10.014"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.00783.x"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgl119"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306220200"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M511052200"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-1484"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1006\/scdb.1997.0151"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.9.5414"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V84.11.3799.bloodjournal84113799"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401030"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2008.08.005"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/35037710"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00005-007-0014-x"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402741"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80054-4"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-005-0111-7"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2005.04.008"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2009.08.016"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21713"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.200700151"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(00)00220-1"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.27"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb00187.x"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.47.120505.105122"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.1012"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0100-879X2003001100013"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1054\/plef.2001.0331"},{"key":"e_1_2_5_30_1","first-page":"5047","article-title":"Induction of apoptosis by arachidonic acid in chronic myeloid leukemia cells","volume":"59","author":"Rizzo MT","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_5_31_1","doi-asserted-by":"crossref","first-page":"3792","DOI":"10.1182\/blood.V88.10.3792.bloodjournal88103792","article-title":"Arachidonic acid mediates interleukin\u20101 and tumor necrosis factor\u2010\u03b1 induced activation of the c\u2010jun amino terminal kinase in stromal cells","volume":"88","author":"Rizzo MT","year":"1996","journal-title":"Blood"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)31674-0"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2009.03.015"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2008.04.004"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1042\/bst025300s"},{"key":"e_1_2_5_36_1","volume-title":"Textbook of Clinical Chemistry","author":"Tietz NW","year":"1994"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2003.08.007"},{"key":"e_1_2_5_38_1","doi-asserted-by":"crossref","unstructured":"Van EttenRA.2007.Aberrant cytokine signaling in leukemia. 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