{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T18:40:25Z","timestamp":1760985625579},"reference-count":36,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2000,3,1]]},"abstract":"<jats:p> Treatment of human leukemia THP-1 cells with bufalin, a specific inhibitor of Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-ATPase, sequentially induces c- fos and inflammatory cytokines interleukin-1\u03b2 (IL-1\u03b2) and tumor necrosis factor-\u03b1 (TNF-\u03b1) gene expressions before the appearance of mature phenotypes of monocytic cells. In this study we examined the signal transduction leading to bufalin-induced gene expressions. Bufalin selectively activated extracellular signal-regulated kinase (ERK), compared with other mitogen-activated protein (MAP) kinase family members. Pretreatment of THP-1 cells with PD-98059, an inhibitor of the ERK-kinase cascade, abolished bufalin-induced c- fos and IL-1\u03b2 gene expressions, indicating that the ERK-kinase cascade mediates the induction of inflammatory cytokines by bufalin. Inhibition of the Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup> exchanger by KB-R7943 and of protein kinase C (PKC) by Ro-31-8220 suppressed ERK activation and gene expressions of c- fos and IL-1\u03b2. These findings suggest that Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-ATPase inhibition by bufalin induces calcium influx and thereby activates PKC and ERK. In cells treated with an inhibitor of p38 MAP kinases, SB-203580, bufalin-mediated ERK activation became persistent and the induction of IL-1\u03b2 and TNF-\u03b1 expressions was significantly augmented. These results suggest that cross talk in bufalin-mediated ERK activation is negatively regulated by endogenous p38 MAP kinase activations. <\/jats:p>","DOI":"10.1152\/ajpcell.2000.278.3.c500","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T22:27:20Z","timestamp":1514154440000},"page":"C500-C508","source":"Crossref","is-referenced-by-count":38,"title":["ERK signaling mediates the induction of inflammatory  cytokines by bufalin in human monocytic cells"],"prefix":"10.1152","volume":"278","author":[{"given":"Masahiro","family":"Kurosawa","sequence":"first","affiliation":[{"name":"Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, Tokyo 142-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Numazawa","sequence":"additional","affiliation":[{"name":"Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, Tokyo 142-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiro","family":"Tani","sequence":"additional","affiliation":[{"name":"Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, Tokyo 142-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takemi","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, Tokyo 142-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(95)00227-Z"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(87)90021-2"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(89)81494-2"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1021\/jm00084a004"},{"key":"B5","first-page":"1","volume":"64","author":"Davis R. J.","year":"1999","journal-title":"Biochem. Soc. Symp."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.17.7686"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)52998-7"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/BF00169051"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041270202"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.1992.tb02966.x"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.37.22391"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1998.tb08987.x"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1993.1936"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1097\/00062752-199603010-00005"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/364249a0"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.44.27723"},{"key":"B17","first-page":"29","volume":"64","author":"Kyriakis J. M.","year":"1999","journal-title":"Biochem. Soc. Symp."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/BFb0030902"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.12.7059"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(85)91310-5"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/315641a0"},{"key":"B22","first-page":"85","volume":"1333","author":"Minden A.","year":"1997","journal-title":"Biochim. Biophys. Acta"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041600114"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(96)00210-9"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/0065-2571(91)90018-H"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/312724a0"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.12.6586"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910260208"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.11.3183"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.24.14067"},{"key":"B31","first-page":"3097","volume":"57","author":"Watabe M.","year":"1997","journal-title":"Cancer Res."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201592"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15708.x"},{"key":"B34","first-page":"259","volume":"14","author":"Watano T.","year":"1998","journal-title":"Can. J. Cardiol."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.83.3.395"},{"key":"B36","first-page":"4634","volume":"52","author":"Zhang L.","year":"1992","journal-title":"Cancer Res."}],"container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.2000.278.3.C500","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T19:07:19Z","timestamp":1718651239000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.2000.278.3.C500"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,3,1]]},"references-count":36,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2000,3,1]]}},"alternative-id":["10.1152\/ajpcell.2000.278.3.C500"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.2000.278.3.c500","relation":{},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,3,1]]}}}