{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:55:57Z","timestamp":1791194157067,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,9,9]],"date-time":"2005-09-09T00:00:00Z","timestamp":1126224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2006,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The aim of this study was to examine whether a neuroprotector, PBN (\u03b1\u2010phenyl\u2010<jats:italic>tert<\/jats:italic>\u2010butyl nitrone), enhances apoptosis induced by hyperthermia, which generates superoxide (O<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tex2gif-stack-1.gif\" xlink:title=\"urn:x-wiley:00219541:media:JCP20482:tex2gif-stack-1\"\/>) intracellularly, since the release of nitric oxide (NO) from PBN under oxidative stress has been reported. When human myelomonocytic lymphoma U937 cells were treated with hyperthermia (44\u00b0C, 10 min) and PBN, an increase in the concentration of nitrite in the culture medium, and a decrease in the hyperthermia\u2010induced production of O<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tex2gif-stack-2.gif\" xlink:title=\"urn:x-wiley:00219541:media:JCP20482:tex2gif-stack-2\"\/> was observed. Imaging using a fluorescence dye for intracellular NO, diaminofluorescein\u20102 diacetate (DAF\u20102 DA), revealed the formation of NO in the apoptotic cells treated with hyperthermia and PBN combined. Apoptotic endpoints were significantly enhanced by the combined treatment: a decrease in mitochondrial trans\u2010membrane potential, cleavage of Bid, release of cytochrome c, and activation of caspase\u20108 and \u20103. An increase in the intracellular Ca<jats:sup>2+<\/jats:sup> concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>), externalization of Fas, and decrease in Hsp70 and phosphorylated HSF1 were observed following the combined treatment. Furthermore, scavengers of NO and ONOO<jats:sup>\u2212<\/jats:sup> significantly inhibited the enhancement of apoptosis, the externalization of Fas and the increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. These results suggest that, (1) NO is released from PBN by hyperthermia, and subsequently reacts with O<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tex2gif-stack-3.gif\" xlink:title=\"urn:x-wiley:00219541:media:JCP20482:tex2gif-stack-3\"\/> to form ONOO<jats:sup>\u2212<\/jats:sup>, (2) NO and ONOO<jats:sup>\u2212<\/jats:sup> are involved in the enhancement of apoptosis through Fas\u2010mitochondria\u2010caspase and [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>\u2010dependent pathways, and (3) a decrease in Hsp70 and phosphorylated HSF1 also contributed to the enhancement of apoptosis. J. Cell. Physiol. 206: 468\u2013476, 2006. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.20482","type":"journal-article","created":{"date-parts":[[2005,9,9]],"date-time":"2005-09-09T22:16:27Z","timestamp":1126304187000},"page":"468-476","source":"Crossref","is-referenced-by-count":33,"title":["Enhancement of apoptosis by nitric oxide released from \u03b1\u2010phenyl\u2010<i>tert<\/i>\u2010butyl nitrone under hyperthermic 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