Source:http://linkedlifedata.com/resource/pubmed/id/20732852
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
9
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pubmed:dateCreated |
2010-8-24
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pubmed:abstractText |
Oxidative stress is one of the major pathogenesis of chronic obstructive pulmonary disease (COPD). gamma-Glutamylcysteine synthetase (gamma-GCS) is one of the paramount antioxidant enzymes in COPD. Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a ligand-activated transcription factor, which is activated by specific ligands such as rosiglitazone (RGZ), exerting multiple biological effects. PPARgamma coactivator-1alpha (PGC-1alpha) is a PPARgamma coactivator, which binds to PPARgamma by induction of PPARgamma ligands, co-activating PPARgamma target genes. Growing evidence has suggested that PPARgamma/PGC-1alpha can regulate multiple antioxidant genes. However, the effect of PPARgamma/PGC-1alpha on gamma-GCS during the development of COPD remains unclear. Here, we measured the expression levels of PPARgamma, PGC-1alpha and gamma-GCS, gamma-GCS activity and reactive oxygen species (ROS) contents in lungs of rats treated by cigarette smoke (CS) + lipopolysaccharide (LPS) and CS + LPS + RGZ, as well as lungs of patients suffered from COPD. Compared with lungs from CS + LPS-treated rats, lungs of RGZ-treated rats demonstrated markedly lower ROS contents, and remarkable increase of gamma-GCS activity and increase of the expression levels of PPARgamma, PGC-1alpha, and gamma-GCS. Furthermore, compared with controls, expression levels of PPARgamma, PGC-1alpha, and gamma-GCS significantly increased in the lungs of mild COPD patients, and progressively decreased in lungs of patients with moderate and severe COPD. gamma-GCS protein was positively correlated with FEV(1)%. PPARgamma and PGC-1alpha proteins were positively correlated with gamma-GCS activity and mRNA level. In conclusion, gamma-GCS showed compensatory upregulation in the early stage of COPD, which progressively decompensate with increasing COPD severity. The activation of the PPARgamma/PGC-1alpha pathway may protect against COPD progression by upregulating gamma-GCS and relieving oxidative stress.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Glutamate-Cysteine Ligase,
http://linkedlifedata.com/resource/pubmed/chemical/Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/PPAR gamma,
http://linkedlifedata.com/resource/pubmed/chemical/PPARGC1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ppargc1a protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/RNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Smoke,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazolidinediones,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/rosiglitazone
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1745-7270
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
42
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
603-14
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pubmed:meshHeading |
pubmed-meshheading:20732852-Aged,
pubmed-meshheading:20732852-Animals,
pubmed-meshheading:20732852-Blotting, Western,
pubmed-meshheading:20732852-Female,
pubmed-meshheading:20732852-Glutamate-Cysteine Ligase,
pubmed-meshheading:20732852-Heat-Shock Proteins,
pubmed-meshheading:20732852-Humans,
pubmed-meshheading:20732852-Immunohistochemistry,
pubmed-meshheading:20732852-In Situ Hybridization,
pubmed-meshheading:20732852-Lipopolysaccharides,
pubmed-meshheading:20732852-Lung,
pubmed-meshheading:20732852-Male,
pubmed-meshheading:20732852-Middle Aged,
pubmed-meshheading:20732852-PPAR gamma,
pubmed-meshheading:20732852-Pulmonary Disease, Chronic Obstructive,
pubmed-meshheading:20732852-RNA-Binding Proteins,
pubmed-meshheading:20732852-Rats,
pubmed-meshheading:20732852-Rats, Sprague-Dawley,
pubmed-meshheading:20732852-Reactive Oxygen Species,
pubmed-meshheading:20732852-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20732852-Signal Transduction,
pubmed-meshheading:20732852-Smoke,
pubmed-meshheading:20732852-Thiazolidinediones,
pubmed-meshheading:20732852-Tobacco,
pubmed-meshheading:20732852-Transcription Factors
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pubmed:year |
2010
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pubmed:articleTitle |
Positive correlation between PPARgamma/PGC-1alpha and gamma-GCS in lungs of rats and patients with chronic obstructive pulmonary disease.
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pubmed:affiliation |
Department of Respiratory Medicine, Hunan Institute of Gerontology, Hunan Province Geriatric Hospital, Changsha, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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