{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:47:04Z","timestamp":1791294424989,"version":"4.1.0"},"reference-count":40,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[1998,1,1]]},"abstract":"<jats:p>Nitric oxide (\u22c5 NO) can be produced within the lung, and recently inhaled nitric oxide has been used as a therapeutic agent. Peroxynitrite<jats:sup>1<\/jats:sup>(ONOO<jats:sup>\u2212<\/jats:sup>), the product of the nearly diffusion-limited reaction between \u22c5 NO and superoxide, may represent the proximal reactive species mediating \u22c5 NO injury to pulmonary cells. To investigate the physiological and pathological reactivities of \u22c5 NO and ONOO<jats:sup>\u2212<\/jats:sup>at the molecular and cellular levels, bovine pulmonary artery endothelial cells (BPAEC) and rat type II epithelial cells were exposed to \u22c5 NO (0.01\u20132.5 \u03bcM\/min for 2 h) generated by spermine-NONOate and papa-NONOate and to the same fluxes of ONOO<jats:sup>\u2212<\/jats:sup>generated by 1,3-morpholinosydnonimine (SIN-1). Exposure to SIN-1 resulted in cellular injury and death in both cell types. Epithelial cells displayed a concentration-dependent loss of cellular viability within 8 h of exposure. In contrast, BPAEC loss of cellular viability was evident after 18 h postexposure. Events preceding cell death in BPAEC include depolarization of the mitochondrial membrane, evident as early as 6 h postexposure, loss of cellular redox activity at 16 h, and DNA fragmentation detected by in situ staining at 18 h after exposure. Exposure of BPAEC to \u22c5 NO did not affect the cellular viability, but type II cells were injured in a manner similar to ONOO<jats:sup>\u2212<\/jats:sup>exposure. \u22c5 NO-mediated cellular injury within type II cells was reduced by preincubation with N-acetylcysteine. The data imply that the pathological and physiological effects of \u22c5 NO may be regulated by its reactions with superoxide and reduced thiols.<\/jats:p>","DOI":"10.1152\/ajplung.1998.274.1.l112","type":"journal-article","created":{"date-parts":[[2017,12,23]],"date-time":"2017-12-23T14:09:20Z","timestamp":1514038160000},"page":"L112-L118","source":"Crossref","is-referenced-by-count":26,"title":["Nitric oxide and peroxynitrite-mediated pulmonary cell death"],"prefix":"10.1152","volume":"274","author":[{"given":"Andrew J.","family":"Gow","sequence":"first","affiliation":[{"name":"Institute for Environmental Medicine and Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen R.","family":"Thom","sequence":"additional","affiliation":[{"name":"Institute for Environmental Medicine and Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Ischiropoulos","sequence":"additional","affiliation":[{"name":"Institute for Environmental Medicine and Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1996.271.5.C1424"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.155.3.9117019"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(96)00240-7"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.16.7162"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1006\/niox.1996.0114"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1996.0178"},{"key":"B7","doi-asserted-by":"crossref","first-page":"29409","DOI":"10.1016\/S0021-9258(18)43894-X","volume":"269","author":"Castro L.","year":"1994","journal-title":"J. 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