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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2006-3-16
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pubmed:abstractText |
Nitric oxide (*NO) was shown to stimulate the proteasomal function and the ubiquitin-proteasome pathway and to ameliorate endothelial apoptotic signaling induced by oxidants. Understanding the regulatory mechanisms by which *NO stimulates proteasomes and affords cytoprotection in endothelial cells has therapeutic implications, as many vascular diseases are characterized by a deficiency in *NO. Here we report that *NO/cGMP/cAMP-induced immunoproteasome subunit expression is responsible for the increased proteasomal activities. Cells pretreated with protein kinase G and protein kinase A inhibitors markedly attenuated *NO-dependent proteasome activation. Results show that the *NO/cGMP/cAMP signaling mechanism enhanced the phosphorylation of the transcription factor cAMP-response element-binding protein, elevated the cAMP-response element-promoter activity and induced the expression of immunoproteasomal subunits (LMP2 and LMP7). *NO-dependent proteasomal activity was abrogated in cells transfected with antisense LMP2 and LMP7 oligonucleotides. Lower levels of LMP2 and LMP7 were detected in aorta of iNOS(-/-) mice compared to wild-type controls, suggesting that endogenous production of *NO is important in the basal regulation of immunoproteasome. The *NO/cGMP/cAMP signaling pathway mitigates transferrin-iron-mediated oxidative stress and apoptosis through induction of immunoproteasomes. These results provide new insights on the regulatory mechanisms by which the *NO-mediated immunoproteasome signaling pathway affords cytoprotection in endothelial cells.
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pubmed:grant |
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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/ATP dependent 26S protease,
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic GMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide,
http://linkedlifedata.com/resource/pubmed/chemical/LMP-2 protein,
http://linkedlifedata.com/resource/pubmed/chemical/LMP7 protein,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0891-5849
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
40
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1034-44
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:16540399-Animals,
pubmed-meshheading:16540399-Antioxidants,
pubmed-meshheading:16540399-Apoptosis,
pubmed-meshheading:16540399-Cattle,
pubmed-meshheading:16540399-Cyclic AMP,
pubmed-meshheading:16540399-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:16540399-Cyclic AMP-Dependent Protein Kinase Type II,
pubmed-meshheading:16540399-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:16540399-Cyclic GMP,
pubmed-meshheading:16540399-Cysteine Endopeptidases,
pubmed-meshheading:16540399-Endothelium, Vascular,
pubmed-meshheading:16540399-Humans,
pubmed-meshheading:16540399-Hydrogen Peroxide,
pubmed-meshheading:16540399-Mice,
pubmed-meshheading:16540399-Mice, Inbred C57BL,
pubmed-meshheading:16540399-Mice, Knockout,
pubmed-meshheading:16540399-Multienzyme Complexes,
pubmed-meshheading:16540399-Nitric Oxide,
pubmed-meshheading:16540399-Nitric Oxide Synthase Type II,
pubmed-meshheading:16540399-Oxidative Stress,
pubmed-meshheading:16540399-Proteasome Endopeptidase Complex,
pubmed-meshheading:16540399-Signal Transduction,
pubmed-meshheading:16540399-Up-Regulation
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pubmed:year |
2006
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pubmed:articleTitle |
Upregulation of immunoproteasomes by nitric oxide: potential antioxidative mechanism in endothelial cells.
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pubmed:affiliation |
Department of Biophysics and Free Radical Research Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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