{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T05:10:08Z","timestamp":1751173808675,"version":"3.41.0"},"reference-count":44,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2001,8,1]]},"abstract":"<jats:p>Pathophysiological stimuli, including hypoxia, lead to K<jats:sup>+<\/jats:sup>efflux from the intracellular lumen to the extracellular space, thereby increasing local tissue K<jats:sup>+<\/jats:sup>concentrations and depolarizing resident cells. In this study, we investigated the effects of increased extracellular K<jats:sup>+<\/jats:sup>concentrations ([K<jats:sup>+<\/jats:sup>]<jats:sub>e<\/jats:sub>) on heat shock protein (HSP) expression in the porcine proximal tubule epithelial cell line LLC-PK<jats:sub>1<\/jats:sub>. We analyzed HSP-25, HSP-72, HSC-73, and HSP-90 protein expression by Western blot analyses and HSP-72 promoter activity by luciferase reporter gene assays using the proximal 1,440 bp of the HSP-72 promoter. Elevating [K<jats:sup>+<\/jats:sup>]<jats:sub>e<\/jats:sub>from 20 to 50 mM increased HSP-72 protein expression and promoter activity but did not affect HSP-25, HSC-73, or HSP-90 levels. Addition of identical concentrations of sodium chloride did not increase HSP-72 expression to a similar amount. The Ca<jats:sup>2+<\/jats:sup>channel blocker diltiazem and the Ca<jats:sup>2+<\/jats:sup>-specific chelator EGTA-AM abolished high [K<jats:sup>+<\/jats:sup>]<jats:sub>e<\/jats:sub>-induced HSP-72 expression by 69.7 and 75.2%, respectively, indicating that the transcriptional induction of HSP-72 involves Ca<jats:sup>2+<\/jats:sup>influx. As measured by confocal microscopy using the Ca<jats:sup>2+<\/jats:sup>dye fluo 3-AM, we also observed a rapid increase of intracellular Ca<jats:sup>2+<\/jats:sup>concentration as early as 30 s after placing LLC-PK<jats:sub>1<\/jats:sub>cells in high [K<jats:sup>+<\/jats:sup>]<jats:sub>e<\/jats:sub>. We further analyzed whether Ca<jats:sup>2+<\/jats:sup>influx was necessary for induction of HSP-72 expression by high [K<jats:sup>+<\/jats:sup>]<jats:sub>e<\/jats:sub>using Ca<jats:sup>2+<\/jats:sup>-free medium. Here, induction of HSP-72 in response to high [K<jats:sup>+<\/jats:sup>]<jats:sub>e<\/jats:sub>was completely abolished. Our data thus demonstrate activation of a protective cellular response to ionic stress, e.g., elevated K<jats:sup>+<\/jats:sup>concentrations, by specifically increasing protein levels of HSP-72.<\/jats:p>","DOI":"10.1152\/ajprenal.2001.281.2.f280","type":"journal-article","created":{"date-parts":[[2017,12,23]],"date-time":"2017-12-23T14:08:31Z","timestamp":1514038111000},"page":"F280-F287","source":"Crossref","is-referenced-by-count":4,"title":["K<sup>+<\/sup>-induced HSP-72 expression is mediated via rapid Ca<sup>2+<\/sup>influx in renal epithelial cells"],"prefix":"10.1152","volume":"281","author":[{"given":"Oliver","family":"Eickelberg","sequence":"first","affiliation":[{"name":"Departments of Pathology, Surgery, and Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520-8023"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Geibel","sequence":"additional","affiliation":[{"name":"Departments of Pathology, 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