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http://purl.uniprot.org/citations/24015256http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24015256http://www.w3.org/2000/01/rdf-schema#comment"The redox-active pyocyanin (PCN) secreted by the respiratory pathogen Pseudomonas aeruginosa generates reactive oxygen species (ROS) and causes oxidative stress to pulmonary epithelial cells. Nuclear factor (erythroid-derived 2)-like 2 (NRF2) confers protection against ROS-mediated cell death by inducing the expression of detoxifying enzymes and proteins via its binding to the cis-acting antioxidant response element (ARE). However, a clear relationship between NRF2 and PCN-mediated oxidative stress has not been established experimentally. In this study, we investigated the induction of NRF2-ARE response by PCN in the pulmonary epithelial cells. We analyzed the effect of PCN on NRF2 expression and nuclear translocation in cultured human airway epithelial cells, and in a mouse model of chronic PCN exposure. NRF2-dependent transcription of antioxidative enzymes was also assessed. Furthermore, we used inhibitors to examine the involvement of EGFR and its downstream signaling components that mediate NRF2-ARE-activation in response to PCN. PCN enhances the nuclear NRF2 accumulation and activates the transcription of ARE-mediated antioxidant genes. Furthermore, PCN activates NRF2 by inducing the EGFR-phosphoinositide-3-kinase (PI3K) signaling pathway and its main downstream effectors, AKT and MEK1/2-ERK1/2 MAP kinases. Inhibition of the EGFR-PI3K signaling markedly attenuates PCN-stimulated NRF2 accumulation in the nucleus. We demonstrate for the first time that PCN-mediated oxidative stress activates the EGFR-PI3K-AKT/MEK1/2-ERK1/2 MAP kinase signaling pathway, leading to nuclear NRF2 translocation and ARE responsiveness in pulmonary epithelial cells."xsd:string
http://purl.uniprot.org/citations/24015256http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0072528"xsd:string
http://purl.uniprot.org/citations/24015256http://purl.uniprot.org/core/author"Hao Y."xsd:string
http://purl.uniprot.org/citations/24015256http://purl.uniprot.org/core/author"Xu Y."xsd:string
http://purl.uniprot.org/citations/24015256http://purl.uniprot.org/core/author"Duan C."xsd:string
http://purl.uniprot.org/citations/24015256http://purl.uniprot.org/core/author"Kuang Z."xsd:string
http://purl.uniprot.org/citations/24015256http://purl.uniprot.org/core/author"Lau G.W."xsd:string
http://purl.uniprot.org/citations/24015256http://purl.uniprot.org/core/author"Jeffries J.L."xsd:string
http://purl.uniprot.org/citations/24015256http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/24015256http://purl.uniprot.org/core/name"PLoS One"xsd:string
http://purl.uniprot.org/citations/24015256http://purl.uniprot.org/core/pages"e72528"xsd:string
http://purl.uniprot.org/citations/24015256http://purl.uniprot.org/core/title"Pseudomonas aeruginosa pyocyanin activates NRF2-ARE-mediated transcriptional response via the ROS-EGFR-PI3K-AKT/MEK-ERK MAP kinase signaling in pulmonary epithelial cells."xsd:string
http://purl.uniprot.org/citations/24015256http://purl.uniprot.org/core/volume"8"xsd:string
http://purl.uniprot.org/citations/24015256http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/24015256
http://purl.uniprot.org/citations/24015256http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/24015256
http://purl.uniprot.org/uniprot/#_E2I973-mappedCitation-24015256http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24015256
http://purl.uniprot.org/uniprot/#_A0A068JD88-mappedCitation-24015256http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24015256
http://purl.uniprot.org/uniprot/#_A8K2T7-mappedCitation-24015256http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24015256
http://purl.uniprot.org/uniprot/#_A0A068JCC9-mappedCitation-24015256http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24015256
http://purl.uniprot.org/uniprot/#_A0A1Y0B9F8-mappedCitation-24015256http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24015256
http://purl.uniprot.org/uniprot/#_A0A1Y0B9F6-mappedCitation-24015256http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24015256
http://purl.uniprot.org/uniprot/#_A0A1Y0B9G5-mappedCitation-24015256http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24015256
http://purl.uniprot.org/uniprot/#_A0A1Y0B9F1-mappedCitation-24015256http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24015256
http://purl.uniprot.org/uniprot/#_B3KVH4-mappedCitation-24015256http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24015256