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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
22
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pubmed:dateCreated |
1999-12-10
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pubmed:abstractText |
Paraquat (PQ) is a well described pneumotoxicant that produces toxicity by redox cycling with cellular diaphorases, thereby elevating intracellular levels of superoxide (O-(2)). NO synthase (NOS) has been shown to participate in PQ-induced lung injury. Current theory holds that NO reacts with O-(2) generated by PQ to produce the toxin peroxynitrite. We asked whether NOS might alternatively function as a PQ diaphorase and reexamined the question of whether NO/O-(2) reactions were toxic or protective. Here, we show that: (i) neuronal NOS has PQ diaphorase activity that inversely correlates with NO formation; (ii) PQ-induced endothelial cell toxicity is attenuated by inhibitors of NOS that prevent NADPH oxidation, but is not attenuated by those that do not; (iii) PQ inhibits endothelium-derived, but not NO-induced, relaxations of aortic rings; and (iv) PQ-induced cytotoxicity is potentiated in cytokine-activated macrophages in a manner that correlates with its ability to block NO formation. These data indicate that NOS is a PQ diaphorase and that toxicity of such redox-active compounds involves a loss of NO-related activity.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-1280257,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-1370373,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-1378626,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-1381691,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-1650215,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-1654835,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-1707173,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-1712077,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-1715579,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-1715581,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-1720773,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-1959661,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-2500125,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-2828357,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-3384345,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-3495737,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-4365647,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-5171564,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-6086882,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-6489882,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-6954885,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-7077538,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-7519778,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-7691109,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-7779464,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-7796872,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-8026798,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-8030904,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-8145361,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-8234317,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-8531085,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-8692893,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-8789949,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-8791092,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-8806874,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-8847437,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-8897905,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-9042951,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-9333325,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-9398256,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-9500851,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10535996-9776960
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
26
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pubmed:volume |
96
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
12760-5
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10535996-Animals,
pubmed-meshheading:10535996-Cell Line,
pubmed-meshheading:10535996-Cell Survival,
pubmed-meshheading:10535996-Endothelium, Vascular,
pubmed-meshheading:10535996-Enzyme Inhibitors,
pubmed-meshheading:10535996-Macrophages,
pubmed-meshheading:10535996-Male,
pubmed-meshheading:10535996-NADH, NADPH Oxidoreductases,
pubmed-meshheading:10535996-Nitric Oxide,
pubmed-meshheading:10535996-Nitric Oxide Synthase,
pubmed-meshheading:10535996-Nitric Oxide Synthase Type I,
pubmed-meshheading:10535996-Paraquat,
pubmed-meshheading:10535996-Rabbits
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pubmed:year |
1999
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pubmed:articleTitle |
A mechanism of paraquat toxicity involving nitric oxide synthase.
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pubmed:affiliation |
Department of Medicine, National Jewish Medical and Research Center, School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO 80206, USA. DAYB@njc.org
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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