{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:43:34Z","timestamp":1789987414680,"version":"4.0.1"},"reference-count":0,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[1997,5,1]]},"abstract":"<jats:p> Toxic bile salts induce hepatocyte apoptosis, a model relevant to liver injury during cholestasis. However, the signaling mechanisms culminating in bile salt-induced apoptosis remain unclear. Because protein kinase C (PKC) is activated by bile salts in hepatocytes and causes apoptosis in other cells, we tested the hypothesis that bile salt-induced hepatocyte apoptosis is mediated by PKC. The PKC inhibitors chelerythrine and Go-6976 reduced, whereas a PKC agonist, phorbol 12-myristate 13-acetate (PMA), increased glycochenodeoxycholate (GCDC)-induced hepatocyte apoptosis. Membrane-associated total PKC activity was increased in GCDC-treated hepatocytes. Quantitative immunoblot analysis demonstrated membrane translocation of PKC-alpha, PKC-delta, and PKC-epsilon to hepatocyte membranes after administration of GCDC. Direct activation of PKC-alpha and PKC-delta by GCDC was also demonstrated using recombinant, baculovirus-expressed PKC isoforms in a medium of defined lipid composition. Chelerythrine and Go-6976 reduced, whereas PMA enhanced, cathepsin B activity during treatment of hepatocytes with GCDC, demonstrating coupling of PKC activity to the protease effector mechanisms of apoptosis. In conclusion, our data suggest for the first time that PKC-dependent signaling pathways play a critical role in bile salt-induced hepatocyte apoptosis. <\/jats:p>","DOI":"10.1152\/ajpgi.1997.272.5.g1109","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T07:35:57Z","timestamp":1514100957000},"page":"G1109-G1115","source":"Crossref","is-referenced-by-count":24,"title":["Bile salt-induced apoptosis of hepatocytes involves activation of protein kinase C"],"prefix":"10.1152","volume":"272","author":[{"given":"B. A.","family":"Jones","sequence":"first","affiliation":[{"name":"Center for Basic Research in Digestive Diseases, Mayo Clinic,Rochester, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. P.","family":"Rao","sequence":"additional","affiliation":[{"name":"Center for Basic Research in Digestive Diseases, Mayo Clinic,Rochester, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. T.","family":"Stravitz","sequence":"additional","affiliation":[{"name":"Center for Basic Research in Digestive Diseases, Mayo Clinic,Rochester, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. J.","family":"Gores","sequence":"additional","affiliation":[{"name":"Center for Basic Research in Digestive Diseases, Mayo Clinic,Rochester, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpgi.1997.272.5.G1109","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T20:32:29Z","timestamp":1567974749000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpgi.1997.272.5.G1109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,5,1]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1997,5,1]]}},"alternative-id":["10.1152\/ajpgi.1997.272.5.G1109"],"URL":"https:\/\/doi.org\/10.1152\/ajpgi.1997.272.5.g1109","relation":{},"ISSN":["0193-1857","1522-1547"],"issn-type":[{"value":"0193-1857","type":"print"},{"value":"1522-1547","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,5,1]]}}}