{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T12:25:51Z","timestamp":1761395151786},"reference-count":38,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2000,8,1]]},"abstract":"<jats:p> Previous work from this laboratory demonstrated that arachidonic acid activates c- junNH<jats:sub>2<\/jats:sub>-terminal kinase (JNK) through oxidative intermediates in a Ca<jats:sup>2+<\/jats:sup>-independent manner (Cui X and Douglas JG. Arachidonic acid activates c- jun N-terminal kinase through NADPH oxidase in rabbit proximal tubular epithelial cells. Proc Natl Acad Sci USA 94: 3771\u20133776, 1997.). We now report that JNK can also be activated via a Ca<jats:sup>2+<\/jats:sup>-dependent mechanism by agents that increase the cytosolic Ca<jats:sup>2+<\/jats:sup> concentration (Ca<jats:sup>2+<\/jats:sup> ionophore A<jats:sub>23187<\/jats:sub>, Ca<jats:sup>2+<\/jats:sup>-ATPase inhibitor thapsigargin) or deplete intracellular Ca<jats:sup>2+<\/jats:sup>stores [intracellular Ca<jats:sup>2+<\/jats:sup> chelator 1,2-bis(2-aminophenoxy)ethane- N,N,N\u2032,N\u2032-tetraacetic acid (BAPTA)-AM]. The activation of JNK by BAPTA-AM occurs despite a decrease in cytosolic Ca<jats:sup>2+<\/jats:sup> concentration as detected by the indicator dye fura 2, but appears to be related to Ca<jats:sup>2+<\/jats:sup>metabolism, because modification of BAPTA with two methyl groups increases not only the chelation affinity for Ca<jats:sup>2+<\/jats:sup>, but also the potency for JNK activation. BAPTA-AM stimulates Ca<jats:sup>2+<\/jats:sup> influx across the plasma membrane, and the resulting local Ca<jats:sup>2+<\/jats:sup> increases are probably involved in activation of JNK because Ca<jats:sup>2+<\/jats:sup> influx inhibitors (SKF-96365, nifedipine) and lowering of the free extracellular Ca<jats:sup>2+<\/jats:sup> concentration with EGTA reduce the BAPTA-induced JNK activation. <\/jats:p>","DOI":"10.1152\/ajpcell.2000.279.2.c403","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T22:45:34Z","timestamp":1514155534000},"page":"C403-C409","source":"Crossref","is-referenced-by-count":4,"title":["Ca<sup>2+<\/sup>-dependent activation of c-<i>jun<\/i> NH<sub>2<\/sub>-terminal kinase in primary rabbit proximal tubule epithelial cells"],"prefix":"10.1152","volume":"279","author":[{"given":"Xiao-Lan","family":"Cui","sequence":"first","affiliation":[{"name":"Division of Hypertension, Departments of Medicine 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