{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T05:10:10Z","timestamp":1746335410197,"version":"3.40.4"},"reference-count":32,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,11,26]],"date-time":"2014-11-26T00:00:00Z","timestamp":1416960000000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31071044"],"award-info":[{"award-number":["31071044"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Activated protein kinase C<jats:italic>\u03b4<\/jats:italic>(PKC<jats:italic>\u03b4<\/jats:italic>) associated with cardiac hypertrophy moves from the cytoplasm to the mitochondria and subsequently triggers the apoptotic signalling pathway. The underlying mechanisms remain unknown. The aim of the present study was to investigate whether mitochondrial translocation of PKC<jats:italic>\u03b4<\/jats:italic>phosphorylates multiple sites of Bcl\u20102, resulting in an imbalance between Bcl\u20102 and Bak or Bax, thus enhancing the susceptibility of hypertrophic cardiomyocytes to angiotensin II (AngII)\u2010induced apoptosis. Chronic pressure overload was induced by transverse aortic constriction (TAC) in rats. The apoptotic rate increased in hypertrophied cardiomyocytes. In AngII\u2010treated hearts (10\u00a0nmol\/L, 60\u00a0min), there was an increase in the number of TERMINAL deoxyribonucleotidyl transferase\u2010mediated<jats:styled-content style=\"fixed-case\">dUTP<\/jats:styled-content>\u2013digoxigenin nick end\u2010labelling (TUNEL)\u2010positive cells; PKC<jats:italic>\u03b4<\/jats:italic>inhibition with 500\u00a0nmol\/L<jats:italic>\u03b4<\/jats:italic>V1\u20101 for 60\u00a0min prevented the AngII\u2010induced increase in apoptosis. In the hypertrophied myocardium, PKC<jats:italic>\u03b4<\/jats:italic>expression increased, whereas that of Bcl\u20102 decreased compared with the synchronous control. Treatment of hearts with 10\u00a0nmol\/L AngII for 60\u00a0min activated PKC<jats:italic>\u03b4<\/jats:italic>and induced translocation of PKC<jats:italic>\u03b4<\/jats:italic>to the mitochondria, where activated PKC<jats:italic>\u03b4<\/jats:italic>facilitated the phosphorylation of Bcl\u20102 at serine\u201087 and serine\u201070 sites. The multisite phosphorylated Bcl\u20102 was released from the mitochondria, and exhibited reduced affinity for Bak and Bax. The imbalance between Bcl\u20102 and Bak\/Bax induced the release of mitochondrial cytochrome<jats:italic>c<\/jats:italic>and then activated the caspase 3 apoptotic pathway during AngII stimulation (10\u00a0nmol\/L, 60\u00a0min) of hypertrophied cardiomyocytes. Inhibition of PKC<jats:italic>\u03b4<\/jats:italic>reduced these effects of AngII. The results suggest that PKC<jats:italic>\u03b4<\/jats:italic>can counteract the anti\u2010apoptotic effect of Bcl\u20102 and may promote cardiomyocyte apoptosis through multisite phosphorylation of Bcl\u20102 in hypertrophied cardiomyocytes.<\/jats:p>","DOI":"10.1111\/1440-1681.12295","type":"journal-article","created":{"date-parts":[[2014,8,12]],"date-time":"2014-08-12T12:39:25Z","timestamp":1407847165000},"page":"891-901","source":"Crossref","is-referenced-by-count":4,"title":["Multisite phosphorylation of Bcl\u20102 via protein kinase C<i>\u03b4<\/i>facilitates apoptosis of hypertrophic cardiomyocytes"],"prefix":"10.1111","volume":"41","author":[{"given":"Juan\u2010Juan","family":"Sheng","sequence":"first","affiliation":[{"name":"Department of Aerospace Physiology Fourth Military Medical University Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Aerospace Physiology 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