{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:49:38Z","timestamp":1787017778498,"version":"build-2736575974"},"reference-count":0,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[1996,10,1]]},"abstract":"<jats:p>Primary intracellular targets for nitric oxide (NO) include nonheme iron-containing enzymes and protein-bound iron. Because NO is an important effector molecule in lung inflammation and endothelial cell-associated iron is critical to numerous forms of oxidant-mediated lung injury, we studied the effects of the NO donor S-nitrosoacetylpenicillamine (SNAP) on heme and iron metabolism in cultured sheep pulmonary artery endothelial cells. SNAP (300 microM) caused a transient increase in heme oxygenase-1 (HO-1) mRNA associated with a fivefold increase in HO activity that was completely blocked by the competitive HO inhibitor, tin protoporphyrin IX (SnPP). SNAP-induced activation of HO caused SnPP-sensitive reduction of activity of the hemoprotein catalase and decrease in heme iron. SNAP caused increases in iron-responsive gene products, ferritin and mitochondrial aconitase, secondary to the release of iron from heme stores via HO induction, since these changes were also sensitive to SNPP. The NO-induced increase in nonheme iron was apparent via electron paramagnetic resonance, where an enhanced SNAP-induced (300 microM for 4 h) g = 2.04 signal (e.g., dinitrosyl-iron-sulfur complex) was noted after exposure to a dose of SNAP (200 microM for 14 h) that in itself did not produce a detectable signal. These data show that exposure of pulmonary endothelial cells to NO results in profound changes in intracellular heme- and nonheme-iron homeostasis and that HO plays a central role in affecting this balance.<\/jats:p>","DOI":"10.1152\/ajplung.1996.271.4.l512","type":"journal-article","created":{"date-parts":[[2017,12,23]],"date-time":"2017-12-23T07:53:04Z","timestamp":1514015584000},"page":"L512-L518","source":"Crossref","is-referenced-by-count":12,"title":["Effect of nitric oxide on heme metabolism in pulmonary artery endothelial cells"],"prefix":"10.1152","volume":"271","author":[{"given":"E. L.","family":"Yee","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Pittsburgh School ofMedicine, Pennsylvania 15261, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. R.","family":"Pitt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Pittsburgh School ofMedicine, Pennsylvania 15261, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. R.","family":"Billiar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Pittsburgh School ofMedicine, Pennsylvania 15261, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. M.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Pittsburgh School ofMedicine, Pennsylvania 15261, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajplung.1996.271.4.L512","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T16:45:51Z","timestamp":1567961151000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajplung.1996.271.4.L512"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,10,1]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1996,10,1]]}},"alternative-id":["10.1152\/ajplung.1996.271.4.L512"],"URL":"https:\/\/doi.org\/10.1152\/ajplung.1996.271.4.l512","relation":{},"ISSN":["1040-0605","1522-1504"],"issn-type":[{"value":"1040-0605","type":"print"},{"value":"1522-1504","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,10,1]]}}}