Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To identify changes in gene expression associated with emphysema, we used differential display to compare RNA extracted from emphysematous lungs with that of unused donor tissues taken at the time of transplant. A differentially expressed sequence was identified corresponding to the 3' end of a novel human complementary DNA (cDNA) of unknown function. The human and mouse cDNA sequences were completed by 5' rapid amplification of cDNA ends. We have named it DEXI for dexamethasone-induced transcript. DEXI messenger RNA (mRNA) was upregulated 147% in emphysematous tissue compared with donor tissue. DEXI mRNA was also upregulated 230% by dexamethasone treatment of A549. The increase in expression of DEXI found in emphysema patients' tissues may be owing to their known treatment with corticosteroids. The human DEXI gene is intronless and the predicted open reading frame encodes a 95-residue acidic protein. Database searches revealed the presence of homologues only in mammals, and a human pseudogene. The protein has a predicted central transmembrane domain and a carboxy-terminal leucine zipper. The human mRNA has a single 1.3-kb transcript. We suggest that the increased expression of DEXI in emphysema may either be relevant to disease progression or be indicative of glucocorticoid responsiveness in treated patients.
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PMID:Cloning of dexamethasone-induced transcript: a novel glucocorticoid-induced gene that is upregulated in emphysema. 1147 84

Nuclear factor, erythroid 2 related factor 2 (Nrf2) belongs to the Cap'n'collar/basic region leucine zipper (CNC-bZIP) transcription factor family, and is activated by diverse oxidants, pro-oxidants, antioxidants, and chemopreventive agents. After phosphorylation and dissociation from the cytoplasmic inhibitor, Kelch-like ECH-associated protein 1 (Keap1), Nrf2 translocates to the nucleus and binds to an antioxidant response element (ARE). Through transcriptional induction of ARE-bearing genes that encode antioxidant-detoxifying proteins, Nrf2 activates cellular rescue pathways against oxidative injury, inflammation/immunity, apoptosis, and carcinogenesis. ARE-driven genes include direct antioxidants (e.g., GPx), thiol metabolism-associated detoxifying enzymes (e.g., GSTs), stress-response genes (e.g., HO-1), and others (e.g., PSMB5). Application of nrf2 germ-line mutant mice elucidated protective roles for Nrf2 in various models of human disorders in the liver, lung, kidney, brain, and circulation. In the lung, deficiency of nrf2 augmented injury caused by bleomycin and environmental oxidants including hyperoxia, diesel exhaust particles, and cigarette smoke. Microarray analyses of lungs from nrf2-deficient and -sufficient mice identified Nrf2-dependent genes that might be critical in pulmonary protection. Observations from these studies highlight the importance of the Nrf2-antioxidant pathway and may provide new therapeutic strategies for acute respiratory distress syndrome, idiopathic pulmonary fibrosis, cancer, and emphysema in which oxidative stress is implicated.
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PMID:Nrf2 defends the lung from oxidative stress. 1648 40