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GEN3VA Reports for these tags

DRUGS_BD2K_LINCS_DCIC_COURSERA

SOFT file
Title / Description The NRF2-KEAP1 pathway is an early responsive gene network in arsenic exposed lymphoblastoid cells
Accession GSE51454
Summary Inorganic arsenic, a major environmental contaminant, has risen as an important health problem worldwide. More detailed identification of the molecular mechanisms associated with iAs exposure would help to establish better strategies for prevention and treatment. Although chronic iAs exposures have been previously studied there is little to no information regarding the early events of exposure to iAs. To better characterize the early mechanisms of iAs exposure we conducted gene expression studies using sublethal doses of iAs at two different time-points. The major transcripts differentially regulated at 2 hrs of iAs exposure included antioxidants, detoxificants and chaperones. Moreover, after 12 hrs of exposure many of the down-regulated genes were associated with DNA replication and S phase cell cycle progression. Interestingly, the most affected biological pathway by both 2 or 12 hrs of iAs exposure were the Nrf2-Keap1 pathway, represented by the highly up-regulated HMOX1 transcript, which is transcriptionally regulated by the transcription factor Nrf2. Additional Nrf2 targets included SQSTM1 and ABCB6, which were not previously associated with acute iAs exposure. Signalling pathways such as interferon, B cell receptor and AhR route were also responsive to acute iAs exposure. Since HMOX1 expression increased early (20 min) and was responsive to low iAs concentrations (0.1 M), this gene could be a suitable early biomarker for iAs exposure. In addition, the novel Nrf2 targets SQSTM1 and ABCB6 could play an important and previously unrecognized role in cellular protection against iAs
Organism Homo sapiens
Platform GPL6244
Normalized False
Parsed SOFT file
Metadata
Differential expression method Characteristic Direction
Cutoff 500
Cell_type Lymphoblastoid cells
Drug_id CID 443495
Drug_name Sodium arsenite - 12hr
Organism Human
Visualizations
Principal Component Analysis
Hierarchical clustering
External Links and Downloads
Gene lists Enrichr L1000CDS2 PAEA Crowdsourcing
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Down
Combined