Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.5.2 (NQO1)
 6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutrophil elastase (NE), a potent neutrophil inflammatory mediator, increases MUC5AC mucin gene expression through undefined pathways involving reactive oxygen species. To determine the source of NE-generated reactive oxygen species, we used pharmacologic inhibitors of oxidoreductases to test whether they blocked NE-regulated MUC5AC mRNA expression. We found that dicumarol, an inhibitor of the NADP(H):quinone oxidoreductase 1 (NQO1), inhibited MUC5AC mRNA expression in A549 lung adenocarcinoma cells and primary normal human bronchial epithelial cells. We further tested the role of NQO1 in mediating NE-induced MUC5AC expression by inhibiting NQO1 expression using short interfering RNA (siRNA). Transfection with siRNA specific for NQO1 suppressed NQO1 expression and significantly abrogated MUC5AC mRNA expression. NE treatment caused lipid peroxidation in A549 cells; this effect was inhibited by pretreatment with dicumarol, suggesting that NQO1 also regulates oxidant stress in A549 cells after NE exposure. NE exposure increased NQO1 protein and activity levels; NQO1 expression and activity were limited to the cytosol and did not translocate to the plasma membrane. Our results indicate that NQO1 has an important role as a key mediator of NE-regulated oxidant stress and MUC5AC mucin gene expression.
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PMID:Regulation of MUC5AC expression by NAD(P)H:quinone oxidoreductase 1. 1739 13

Smoking is a substantial risk factor for many respiratory diseases. This study aimed to identify the gene and microRNA changes related to smoking in human airway epithelium by bioinformatics analysis.From the Gene Expression Omnibus (GEO) database, the mRNA datasets GSE11906, GSE22047, GSE63127, and microRNA dataset GSE14634 were downloaded, and were analyzed using GEO2R. Functional enrichment analysis of the differentially expressed genes (DEGs) was enforced using DAVID. The protein-protein interaction (PPI) network and differentially expressed miRNAs (DEMs)- DEGs network were executed by Cytoscape.In total, 107 DEGs and 10 DEMs were determined. Gene Ontology (GO) analysis revealed that DEGs principally enriched in oxidation-reduction process, extracellular space and oxidoreductase activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway demonstrated that DEGs were principally enriched in metabolism of xenobiotics by cytochrome P450 and chemical carcinogenesis. The PPI network revealed 15 hub genes, including NQO1, CYP1B1, AKR1C1, CYP1A1, AKR1C3, CEACAM5, MUCL1, B3GNT6, MUC5AC, MUC12, PTGER4, CALCA, CBR1, TXNRD1, and CBR3. Cluster analysis showed that these hub genes were associated with adenocarcinoma in situ, squamous cell carcinoma, cell differentiation, inflammatory response, oxidative DNA damage, oxidative stress response and tumor necrosis factor. Hsa-miR-627-5p might have the most target genes, including ITLN1, TIMP3, PPP4R4, SLC1A2, NOVA1, RNFT2, CLDN10, TMCC3, EPHA7, SRPX2, PPP1R16B, GRM1, HS3ST3A1, SFRP2, SLC7A11, and KLHDC8A.We identified several molecular changes induced by smoking in human airway epithelium. This study may provide some candidate genes and microRNAs for assessing the risk of lung diseases caused by smoking.
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PMID:Identification of gene and microRNA changes in response to smoking in human airway epithelium by bioinformatics analyses. 3156 4