{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:12:10Z","timestamp":1762175530465,"version":"3.40.4"},"reference-count":20,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2003,1,1]],"date-time":"2003-01-01T00:00:00Z","timestamp":1041379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2003,1,1]],"date-time":"2003-01-01T00:00:00Z","timestamp":1041379200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Nephrol"],"published-print":{"date-parts":[[2003]]},"abstract":"<i>Background:<\/i> Pyelonephritis is a risk factor for renal tubular epithelial cell damage. Recent studies have shown that <i>Escherichia coli<\/i> and\/or its toxins may stimulate apoptotic cell death in renal tubular cells, but the underlying molecular mechanisms remain to be elucidated. <i>Methods:<\/i> Confluent LLC-PK<sub>1<\/sub> cells were exposed to <i>E.\u00a0coli<\/i> toxins from overnight cultures of the uropathogenic O6K13H1 (O6) and the nonpathogenic W3110. The cell death was studied with morphological and biological assay. <i>Results:<\/i><i>E. coli<\/i> soluble toxins from uropathogenic O6:K13:H1(O6) strain were found to induce apoptosis in a dose- and time-dependent manner in LLC-PK1 cells. The expression of FasR and the phosphorylation of ERK1\/2 were significantly upregulated by O6 soluble toxins in a time-dependent manner. Cell death was completely inhibited by two specific ERK1\/2 inhibitors, but not by a broad caspase inhibitor, zVAD-fmk, implicating a caspase-independent pathway via ERK. Moreover, we found that lysophosphatidic acid could trigger a survival signal through G-proteins and PI3K. <i>Conclusion:<\/i> We demonstrate that apoptosis induced by uropathogenic <i>E.\u00a0coli<\/i> toxins is dependent on ERK1\/2. Caspases, although being activated, are not necessary for cell death, and they act after the ERK signaling at which point cells become committed to cell death or can be rescued.<\/jats:p>","DOI":"10.1159\/000069853","type":"journal-article","created":{"date-parts":[[2003,4,15]],"date-time":"2003-04-15T10:10:37Z","timestamp":1050401437000},"page":"140-151","source":"Crossref","is-referenced-by-count":20,"title":["Uropathogenic <i>Escherichia coli<\/i> Toxins Induce Caspase-Independent Apoptosis in Renal Proximal Tubular Cells via ERK Signaling"],"prefix":"10.1159","volume":"23","author":[{"given":"Ming","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timo","family":"Jahnukainen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjie","family":"Bao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Dar\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Ceccatelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianni","family":"Celsi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2003,5,16]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5393.1494"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038\/35015091"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.53.1.155"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.136.1.215"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M102671200"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M004583200"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1038\/356397a0"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.13.4587-4597.2002"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.8.4669-4677.2002"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(02)03193-9"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1042\/0264-6021:3520135"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.9.5233"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5288.780"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.12.7018-7027.2000"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010384200"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.37.26563"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(01)02651-5"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1038\/35069004"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1038\/17135"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1042\/CS20000045"}],"container-title":["American Journal of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/69853","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/69853","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T03:14:52Z","timestamp":1745464492000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000069853"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003]]},"references-count":20,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2003,6,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000069853","archive":["Portico"],"relation":{},"ISSN":["0250-8095","1421-9670"],"issn-type":[{"type":"print","value":"0250-8095"},{"type":"electronic","value":"1421-9670"}],"subject":[],"published":{"date-parts":[[2003]]}}}