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Series GSE11630 Query DataSets for GSE11630
Status Public on Jun 03, 2008
Title HOCL induced airway epithelial gene expression
Organism Homo sapiens
Experiment type Expression profiling by array
Summary In inflammatory diseases of the airway, a high level (estimated to be as high as 8 mM) of HOCl can be generated through a reaction catalyzed by the leukocyte granule enzyme myeloperoxidase (MPO). HOCl, a potent oxidative agent, causes extensive tissue injury through its reaction with various cellular substances, including thiols, nucleotides, and amines. In addition to its physiological source, HOCl can also be generated by chlorine gas inhalation from an accident or a potential terrorist attack. Despite the important role of HOCl-induced airway epithelial injury, the underlying molecular mechanism is largely unknown. In the present study, we found that HOCl induced dose-dependent toxicity in airway epithelial cells. By transcription profiling using GeneChip, we identified a battery of HOCl-inducible antioxidant genes, all of which have been reported previously to be regulated by nuclear factor erythroid-related factor 2 (Nrf2), a transcription factor that is critical to the lung antioxidant response. Consistent with this finding, Nrf2 was found to be activated time and dose dependently by HOCl. Although the epidermal growth factor receptor-MAPK pathway was also highly activated by HOCl, it was not involved in Nrf2 activation and Nrf2-dependent gene expression. Instead, HOCl-induced cellular oxidative stress appeared to lead directly to Nrf2 activation. To further understand the functional significance of Nrf2 activation, small interference RNA was used to knock down Nrf2 level by targeting Nrf2 or enhance nuclear accumulation of Nrf2 by targeting its endogenous inhibitor Keap1. By both methods, we conclude that Nrf2 directly protects airway epithelial cells from HOCl-induced toxicity.
 
Overall design This is genechip study. Detailed study design is described in: Am J Physiol Lung Cell Mol Physiol. 2008 Mar;294(3):L469-77. Epub 2007 Dec 21.
 
Contributor(s) Zhu L, Pi J, Wachi S, Zndersen ME, Wu R, Chen Y
Citation(s) 18156441
Submission date Jun 02, 2008
Last update date Dec 06, 2018
Contact name Yin Chen
E-mail(s) yinchen@thehamner.org
Phone 919-558-1320
Organization name Hamner Institutes for Health Sciences
Department Division of Translational Biology
Street address 6 Davis Dr.
City Research Triangle Park
State/province NC
ZIP/Postal code 27709
Country USA
 
Platforms (1)
GPL571 [HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array
Samples (32)
GSM245427 human cellular RNA_primary airway epithelial cells_tracheobronchial _H511_6h_0.4mM_HG-U133A_2_YCHSUP501
GSM245428 human cellular RNA_primary airway epithelial cells_tracheobronchial _H511_6h_1mM_HG-U133A_2_YCHSUP501
GSM245429 human cellular RNA_primary airway epithelial cells_tracheobronchial _H511_6h_4mM_HG-U133A_2_YCHSUP501
Relations
BioProject PRJNA106147

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE11630_RAW.tar 63.8 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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