{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T17:54:57Z","timestamp":1772819697819,"version":"3.50.1"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2000,8,1]],"date-time":"2000-08-01T00:00:00Z","timestamp":965088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We previously showed that NO induces apoptosis in thymocytes via a p53-dependent pathway. In the present study, we investigated the role of caspases in this process. The pan-caspase inhibitor, ZVAD-fmk, and the caspase-1 inhibitor, Ac-YVAD-cho, both inhibited NO-induced thymocyte apoptosis in a dose-dependent manner, whereas the caspase-3 inhibitor, Ac-DEVD-cho, had little effect even at concentrations up to 500 \u03bcM. ZVAD-fmk and Ac-YVAD-cho were able to inhibit apoptosis when added up to 12 h, but not 16 h, after treatment with the NO donor S-nitroso-N-acetyl penicillamine (SNAP). Caspase-1 activity was up-regulated at 4 h and 8 h and returned to baseline by 24 h; caspase-3 activity was not detected. Cytosolic fractions from SNAP-treated thymocytes cleaved the inhibitor of caspase-activated deoxyribonuclease. Such cleavage was completely blocked by Ac-YVAD-cho, but not by Ac-DEVD-cho or DEVD-fmk. Poly(ADP-ribose) polymerase (PARP) was also cleaved in thymocytes 8 h and 12 h after SNAP treatment; addition of Ac-YVAD-cho to the cultures blocked PARP cleavage. Furthermore, SNAP induced apoptosis in 44% of thymocytes from wild-type mice; thymocytes from caspase-1 knockout mice were more resistant to NO-induced apoptosis. These data suggest that NO induces apoptosis in thymocytes via a caspase-1-dependent but not caspase-3-dependent pathway. Caspase-1 alone can cleave inhibitor of caspase-activated deoxyribonuclease and lead to DNA fragmentation, thus providing a novel pathway for NO-induced thymocyte apoptosis.<\/jats:p>","DOI":"10.4049\/jimmunol.165.3.1252","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T17:16:28Z","timestamp":1398186988000},"page":"1252-1258","source":"Crossref","is-referenced-by-count":40,"title":["Nitric Oxide Induces Thymocyte Apoptosis Via a Caspase-1-Dependent Mechanism"],"prefix":"10.1093","volume":"165","author":[{"given":"Xin","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Pittsburgh School of Medicine, and Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA 15213"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherilyn A","family":"Gordon","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Pittsburgh School of Medicine, and Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA 15213"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-Myeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Pittsburgh School of Medicine, and Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA 15213"},{"name":"Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University , Chunchon, Kangwon-do ,","place":["Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosemary A","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Pittsburgh School of Medicine, and Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA 15213"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Pittsburgh School of Medicine, and Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA 15213"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Ru","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Pittsburgh School of Medicine, and Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA 15213"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard L","family":"Simmons","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Pittsburgh School of Medicine, and Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA 15213"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henri R","family":"Ford","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Pittsburgh School of Medicine, and Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA 15213"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2000,8,1]]},"reference":[{"key":"2026020213082649500_R1","first-page":"5080","volume-title":"J. Immunol.","year":"1993"},{"key":"2026020213082649500_R2","first-page":"3577","volume-title":"J. Immunol.","year":"1996"},{"key":"2026020213082649500_R3","first-page":"2858","volume-title":"J. Immunol.","year":"1995"},{"key":"2026020213082649500_R4","first-page":"88","volume-title":"J. Neurochem.","year":"1998"},{"key":"2026020213082649500_R5","first-page":"4696","volume-title":"J. Immunol.","year":"1997"},{"key":"2026020213082649500_R6","first-page":"73","volume-title":"Annu. Rev. Immunol.","year":"1996"},{"key":"2026020213082649500_R7","first-page":"5876","volume-title":"EMBO J.","year":"1996"},{"key":"2026020213082649500_R8","first-page":"345","volume-title":"Immunology","year":"1998"},{"key":"2026020213082649500_R9","first-page":"1","volume-title":"Biochem J.","year":"1997"},{"key":"2026020213082649500_R10","first-page":"1312","volume-title":"Science","year":"1998"},{"key":"2026020213082649500_R11","first-page":"641","volume-title":"Cell.","year":"1993"},{"key":"2026020213082649500_R12","first-page":"768","volume-title":"Nature","year":"1992"},{"key":"2026020213082649500_R13","first-page":"97","volume-title":"Science","year":"1992"},{"key":"2026020213082649500_R14","first-page":"78","volume-title":"Nature","year":"1995"},{"key":"2026020213082649500_R15","first-page":"81","volume-title":"Nature","year":"1995"},{"key":"2026020213082649500_R16","first-page":"2396","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1999"},{"key":"2026020213082649500_R17","first-page":"32895","volume-title":"J. Biol. Chem.","year":"1998"},{"key":"2026020213082649500_R18","first-page":"15","volume-title":"Mol. Cell. Biochem.","year":"1994"},{"key":"2026020213082649500_R19","first-page":"801","volume-title":"Cell","year":"1995"},{"key":"2026020213082649500_R20","first-page":"28549","volume-title":"J. Biol. Chem.","year":"1998"},{"key":"2026020213082649500_R21","first-page":"43","volume-title":"Nature","year":"1998"},{"key":"2026020213082649500_R22","first-page":"96","volume-title":"Nature","year":"1998"},{"key":"2026020213082649500_R23","first-page":"373","volume-title":"FEBS Lett.","year":"1997"},{"key":"2026020213082649500_R24","first-page":"31138","volume-title":"J. Biol. Chem.","year":"1997"},{"key":"2026020213082649500_R25","first-page":"4122","volume-title":"J. Immunol.","year":"1998"},{"key":"2026020213082649500_R26","first-page":"543","volume-title":"Transplantation","year":"1992"},{"key":"2026020213082649500_R27","first-page":"18715","volume-title":"J. Biol. Chem.","year":"1995"},{"key":"2026020213082649500_R28","first-page":"419","volume-title":"Biochem. Biophys. Res. Commun.","year":"1997"},{"key":"2026020213082649500_R29","first-page":"651","volume-title":"Science","year":"1999"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/165\/3\/1252\/62131292\/1252.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/165\/3\/1252\/62131292\/1252.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T18:13:05Z","timestamp":1770055985000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/165\/3\/1252\/8038493"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,8,1]]},"references-count":29,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2000,8,1]]},"published-print":{"date-parts":[[2000,8,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.165.3.1252","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2000,8]]},"published":{"date-parts":[[2000,8,1]]}}}