{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T19:33:42Z","timestamp":1773084822428,"version":"3.50.1"},"reference-count":36,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2003,6,1]]},"abstract":"<jats:p> Although mitochondrial ATP-sensitive potassium (mitoK<jats:sub>ATP<\/jats:sub>) channels have been reported to reduce the extent of apoptosis, the critical timing of mitoK<jats:sub>ATP<\/jats:sub> channel opening required to protect myocytes against apoptosis remains unclear. In the present study, we examined whether the mitoK<jats:sub>ATP<\/jats:sub> channel serves as a trigger of cardioprotection against apoptosis induced by oxidative stress. Apoptosis of cultured neonatal rat cardiomyocytes was determined by flow cytometry (light scatter and propidium iodide\/annexin V-FITC fluorescence) and by nuclear staining with Hoechst 33342. Mitochondrial membrane potential (\u0394\u03a8) was measured by flow cytometry of cells stained with rhodamine-123 (Rh-123). Exposure to H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> (500 \u03bcM) induced apoptosis, and the percentage of apoptotic cells increased progressively and peaked at 2 h. This H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>-induced apoptosis was associated with the loss of \u0394\u03a8, and the time course of decrease in Rh-123 fluorescence paralleled that of apoptosis. Pretreatment of cardiomyocytes with diazoxide (100 \u03bcM), a putative mitoK<jats:sub>ATP<\/jats:sub> channel opener, for 30 min before exposure to H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> elicited transient and mild depolarization of \u0394\u03a8 and consequently suppressed both apoptosis and \u0394\u03a8 loss after 2-h exposure to H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>. These protective effects of diazoxide were abrogated by the mitoK<jats:sub>ATP<\/jats:sub> channel blocker 5-hydroxydecanoate (500 \u03bcM) but not by the sarcolemmal K<jats:sub>ATP<\/jats:sub> channel blocker HMR-1098 (30 \u03bcM). Our results suggest for the first time that diazoxide-induced opening of mitoK<jats:sub>ATP<\/jats:sub> channels triggers cardioprotection against apoptosis induced by oxidative stress in rat cardiomyocytes. <\/jats:p>","DOI":"10.1152\/ajpheart.01073.2002","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T20:10:01Z","timestamp":1425413401000},"page":"H2235-H2241","source":"Crossref","is-referenced-by-count":41,"title":["Diazoxide triggers cardioprotection against apoptosis  induced by oxidative stress"],"prefix":"10.1152","volume":"284","author":[{"given":"Masashi","family":"Ichinose","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Oita Medical University, Oita 879-5593, Japan; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidetoshi","family":"Yonemochi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Oita Medical University, Oita 879-5593, Japan; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiaki","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsunori","family":"Saikawa","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Oita Medical University, Oita 879-5593, Japan; 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