{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:59:24Z","timestamp":1789970364890,"version":"4.0.1"},"reference-count":31,"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":[[2001,3,1]]},"abstract":"<jats:p> Bufalin, an Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-ATPase inhibitor, simultaneously induced cell differentiation and apoptosis in human monocytic leukemia THP-1 cells. In this study, we investigated the regulatory role of protein kinase C (PKC) isozymes in bufalin-induced cell differentiation and apoptosis. A PKC-specific but isozyme-nonselective inhibitor, Ro-31\u20138220, and a cPKC selective inhibitor, G\u00f6-6976, caused significant attenuation of bufalin-induced interleukin-1\u03b2 (IL-1\u03b2) gene expression, a mature monocytic marker, indicating that cPKC participates in the bufalin-induced cell differentiation. On the other hand, cPKC\u03b2- and nPKC\u03b4-defective THP-1\/TPA cells displayed strong resistance to the bufalin-induced DNA ladder formation. Rottlerin, an nPKC\u03b4-specific inhibitor, partially attenuated preapoptotic effects of bufalin, such as the limited proteolysis of nPKC\u03b4 and poly(ADP-ribose) polymerase and the cell staining by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, suggesting that nPKC\u03b4 is involved, at least in part, in bufalin-induced apoptosis. In contrast, G\u00f6-6976 and rottlerin significantly augmented bufalin-induced apoptosis and differentiation, respectively. The findings suggest that bufalin-induced cell differentiation and apoptosis are interlinked and that distinct PKC isozymes are involved in the fate of the cell. <\/jats:p>","DOI":"10.1152\/ajpcell.2001.280.3.c459","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T20:24:39Z","timestamp":1514147079000},"page":"C459-C464","source":"Crossref","is-referenced-by-count":31,"title":["Distinct PKC isozymes regulate bufalin-induced differentiation and apoptosis in human monocytic cells"],"prefix":"10.1152","volume":"280","author":[{"given":"Masahiro","family":"Kurosawa","sequence":"first","affiliation":[{"name":"Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, Tokyo 142-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Tani","sequence":"additional","affiliation":[{"name":"Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, Tokyo 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