Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2010-8-24
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1745-7270
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
603-14
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
pubmed:year
2010
pubmed:articleTitle
Positive correlation between PPARgamma/PGC-1alpha and gamma-GCS in lungs of rats and patients with chronic obstructive pulmonary disease.
pubmed:affiliation
Department of Respiratory Medicine, Hunan Institute of Gerontology, Hunan Province Geriatric Hospital, Changsha, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't