{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:16:45Z","timestamp":1788931005193,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,1,23]],"date-time":"2012-01-23T00:00:00Z","timestamp":1327276800000},"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":[[2012,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The goal of the present study is to explore the contribution of tumor necrosis factor\u2010\u03b1 (TNF\u03b1)\u2010related pathway to the cytotoxicity of arecoline on human leukemia K562 cells. Arecoline treatment induced death of K562 cells and increased surface expression of TNF\u03b1, TNFR1, and TNFR2. Unlike that of TNFR1 mRNA, transcriptional levels of TNF\u03b1 and TNFR2 mRNA increased in arecoline\u2010treated cells. Moreover, arecoline\u2010induced down\u2010regulation of ADAM17 maturation was involved in surface up\u2010modulation of TNFR1, TNFR2, and TNF\u03b1. Arecoline\u2010elicited increase in intracellular Ca<jats:sup>2+<\/jats:sup> concentration was responsible for JNK\/c\u2010Jun pathway activation and ERK inactivation. Abolition of JNK\/c\u2010Jun pathway suppressed arecoline\u2010induced increase in transcriptional level of TNF\u03b1 and TNFR2 mRNA. TNF\u03b1 and TNFR2 promoter luciferase activity and chromatin immunoprecipitating analyses revealed that c\u2010Jun increasingly bound with TNF\u03b1 and TNFR2 promoter upon arecoline treatment. Over\u2010expression of constitutively active MEK1 abolished the effect of arecoline on suppressing ADAM17 maturation. Pretreatment with TNFR2 antibody abrogated arecoline\u2010induced increased susceptibility of K562 cells for the cytotoxicity of TNF\u03b1 and arecoline\u2010induced cell death. Taken together, our data suggest that up\u2010modulation of TNFR2 surface expression is associated with arecoline\u2010induced death of K562 cells. J. Cell. Physiol. 227: 2240\u20132251, 2012. \u00a9 2011 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jcp.22963","type":"journal-article","created":{"date-parts":[[2011,8,1]],"date-time":"2011-08-01T13:42:32Z","timestamp":1312206152000},"page":"2240-2251","source":"Crossref","is-referenced-by-count":21,"title":["Arecoline\u2010induced death of human leukemia K562 cells is associated with surface up\u2010modulation of 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