Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-1-14
pubmed:abstractText
Hypoxia-inducible factor-1? (HIF-1?) has been reported to regulate over 100 gene expressions in response to hypoxia and other stress conditions. In the present study, we found that arsenite could induce HIF-1? protein accumulation in both mouse epidermal Cl41 cells and mouse embryonic fibroblasts (MEFs). Knockout of p85?, a regulatory subunit of PI-3K, in MEFs (p85?(-/-)) dramatically decreased the arsenite-induced HIF-1? accumulation, indicating that p85? is crucial for arsenite effects on the stabilization of HIF-1? protein. Our further studies suggest that arsenite could induce inducible Hsp70 expression, and transfection of inducible Hsp70 into p85?(-/-) MEFs could restore HIF-1? protein accumulation. Moreover, the results using EMSA and Supershift assays indicate that p85? is crucial for arsenite-induced activation of the heat-shock transcription factor 1 (HSF-1), which is responsible for transcription of inducible Hsp70. Taken together, p85?-mediated HIF-1? stabilization upon arsenite exposure is specifically through HSF-1 activation and subsequent up-regulation of the inducible Hsp70 expression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Arsenites, http://linkedlifedata.com/resource/pubmed/chemical/Carcinogens, http://linkedlifedata.com/resource/pubmed/chemical/Class Ia Phosphatidylinositol..., http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/HSP70 Heat-Shock Proteins, http://linkedlifedata.com/resource/pubmed/chemical/HSP90 Heat-Shock Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Hsf1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha..., http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt, http://linkedlifedata.com/resource/pubmed/chemical/Teratogens, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/arsenite
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1420-9071
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
68
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
475-88
pubmed:meshHeading
pubmed-meshheading:20835880-Animals, pubmed-meshheading:20835880-Arsenites, pubmed-meshheading:20835880-Carcinogens, pubmed-meshheading:20835880-Cell Line, pubmed-meshheading:20835880-Cell Nucleolus, pubmed-meshheading:20835880-Class Ia Phosphatidylinositol 3-Kinase, pubmed-meshheading:20835880-DNA-Binding Proteins, pubmed-meshheading:20835880-Epidermis, pubmed-meshheading:20835880-Fibroblasts, pubmed-meshheading:20835880-Gene Expression Regulation, pubmed-meshheading:20835880-HSP70 Heat-Shock Proteins, pubmed-meshheading:20835880-HSP90 Heat-Shock Proteins, pubmed-meshheading:20835880-Hypoxia-Inducible Factor 1, alpha Subunit, pubmed-meshheading:20835880-Mice, pubmed-meshheading:20835880-Protein Stability, pubmed-meshheading:20835880-Protein Transport, pubmed-meshheading:20835880-Proto-Oncogene Proteins c-akt, pubmed-meshheading:20835880-Teratogens, pubmed-meshheading:20835880-Transcription Factors, pubmed-meshheading:20835880-Up-Regulation
pubmed:year
2011
pubmed:articleTitle
Arsenite stabilizes HIF-1? protein through p85?-mediated up-regulation of inducible Hsp70 protein expression.
pubmed:affiliation
Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural