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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2003-4-17
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pubmed:abstractText |
Heme oxygenase-1 (HO-1) is a cytoprotective enzyme, the expression of which is highly sensitive to induction by pro-oxidant stimuli including the substrate heme and reactive oxygen species. Conceptually, the perception that HO-1 plays a key role in response to oxidative damage is paralleled by evidence showing high expression of HO-1 in a variety of cell systems challenged with nitric oxide (NO) or NO-derivatives, thus revealing a potential biological function for HO-1 against nitrosative stress. In this study, we report that exposure of cardiac cells to hemin (5-20 microM) in combination with compounds that liberate nitroxyl (HNO/NO-) or release NO significantly potentiates HO-1 mRNA and protein expression leading to a remarkable increase in heme oxygenase activity under both normoxic and hypoxic conditions. The amplification of the heme oxygenase pathway appears to involve a direct interaction between heme and the NO groups, as the ability of both NO(-)- and NO-releasing agents to induce HO-1 is totally lost by their pre-incubation for 1 hr in complete medium prior to cell treatment but is highly preserved by addition of hemin during the preincubation step. In addition, we show that the redox-sensitive transcription factor Nrf2 is highly expressed in the nuclear fraction of cells exposed to the NO- generator and that this effect is totally abolished by the presence of N-acetyl-L-cysteine. Interestingly, the expression of Nrf2 is gradually intensified by treating cells with a combination of the NO- releaser and increasing concentrations of hemin. Thus, a strict parallelism exists between the extent of HO-1 induction and expression of Nrf2 elicited by the heme-NO interaction. We propose that modification of the iron protoporphyrin centers by NO groups to modulate HO-1 expression might be regarded as a molecular switch to maximize heme oxygenase enzymatic activity and consequently mitigate the redox imbalance imposed by oxidative and nitrosative stress.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Anions,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Heme,
http://linkedlifedata.com/resource/pubmed/chemical/Heme Oxygenase (Decyclizing),
http://linkedlifedata.com/resource/pubmed/chemical/Heme Oxygenase-1,
http://linkedlifedata.com/resource/pubmed/chemical/Hemin,
http://linkedlifedata.com/resource/pubmed/chemical/NF-E2-Related Factor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Nfe2l2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrogen,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfhydryl Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0145-5680
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
48
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
885-94
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12699247-Acetylcysteine,
pubmed-meshheading:12699247-Animals,
pubmed-meshheading:12699247-Anions,
pubmed-meshheading:12699247-Blotting, Western,
pubmed-meshheading:12699247-Cell Line,
pubmed-meshheading:12699247-Cell Survival,
pubmed-meshheading:12699247-DNA-Binding Proteins,
pubmed-meshheading:12699247-Dose-Response Relationship, Drug,
pubmed-meshheading:12699247-Heme,
pubmed-meshheading:12699247-Heme Oxygenase (Decyclizing),
pubmed-meshheading:12699247-Heme Oxygenase-1,
pubmed-meshheading:12699247-Hemin,
pubmed-meshheading:12699247-Myocardium,
pubmed-meshheading:12699247-NF-E2-Related Factor 2,
pubmed-meshheading:12699247-Nitric Oxide,
pubmed-meshheading:12699247-Nitrogen,
pubmed-meshheading:12699247-Oxidants,
pubmed-meshheading:12699247-Oxidation-Reduction,
pubmed-meshheading:12699247-Oxidative Stress,
pubmed-meshheading:12699247-Oxygen,
pubmed-meshheading:12699247-Protein Binding,
pubmed-meshheading:12699247-RNA,
pubmed-meshheading:12699247-RNA, Messenger,
pubmed-meshheading:12699247-Rats,
pubmed-meshheading:12699247-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:12699247-Sulfhydryl Compounds,
pubmed-meshheading:12699247-Temperature,
pubmed-meshheading:12699247-Time Factors,
pubmed-meshheading:12699247-Trans-Activators
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pubmed:year |
2002
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pubmed:articleTitle |
Interaction of heme with nitroxyl or nitric oxide amplifies heme oxygenase-1 induction: involvement of the transcription factor Nrf2.
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pubmed:affiliation |
Vascular Biology Unit, Department of Surgical Research, Northwick Park Institute for Medical Research, Harrow, Middlesex, HA1 3UJ, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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