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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4 Pt 1
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pubmed:dateCreated |
1996-12-16
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pubmed:abstractText |
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.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Catalase,
http://linkedlifedata.com/resource/pubmed/chemical/Ferritins,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Heme,
http://linkedlifedata.com/resource/pubmed/chemical/Heme Oxygenase (Decyclizing),
http://linkedlifedata.com/resource/pubmed/chemical/Iron,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitroso Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/S-Nitrosoglutathione
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0002-9513
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
271
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
L512-8
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8897897-Animals,
pubmed-meshheading:8897897-Catalase,
pubmed-meshheading:8897897-Cells, Cultured,
pubmed-meshheading:8897897-Electron Spin Resonance Spectroscopy,
pubmed-meshheading:8897897-Endothelium, Vascular,
pubmed-meshheading:8897897-Ferritins,
pubmed-meshheading:8897897-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:8897897-Glutathione,
pubmed-meshheading:8897897-Heme,
pubmed-meshheading:8897897-Heme Oxygenase (Decyclizing),
pubmed-meshheading:8897897-Iron,
pubmed-meshheading:8897897-Nitric Oxide,
pubmed-meshheading:8897897-Nitroso Compounds,
pubmed-meshheading:8897897-Pulmonary Artery,
pubmed-meshheading:8897897-RNA, Messenger,
pubmed-meshheading:8897897-S-Nitrosoglutathione,
pubmed-meshheading:8897897-Sheep
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pubmed:year |
1996
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pubmed:articleTitle |
Effect of nitric oxide on heme metabolism in pulmonary artery endothelial cells.
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pubmed:affiliation |
Department of Pharmacology, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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