Mechanism of sodium arsenite-mediated induction of heme oxygenase-1 in hepatoma cells. Role of mitogen-activated protein kinases
UMass Chan AffiliationsHoward Hughes Medical Institute and Program in Molecular Medicine
Department of Biochemistry and Molecular Biology
Document TypeJournal Article
Calcium-Calmodulin-Dependent Protein Kinases
Gene Expression Regulation, Neoplastic
Heme Oxygenase (Decyclizing)
JNK Mitogen-Activated Protein Kinases
*Mitogen-Activated Protein Kinases
Molecular Sequence Data
Recombinant Fusion Proteins
Transcription Factor AP-1
Tumor Cells, Cultured
p38 Mitogen-Activated Protein Kinases
Medicine and Health Sciences
MetadataShow full item record
AbstractHeme oxygenase-1 is an inducible enzyme that catalyzes heme degradation and has been proposed to play a role in protecting cells against oxidative stress-related injury. We investigated the induction of heme oxygenase-1 by the tumor promoter arsenite in a chicken hepatoma cell line, LMH. We identified a heme oxygenase-1 promoter-driven luciferase reporter construct that was highly and reproducibly expressed in response to sodium arsenite treatment. This construct was used to investigate the role of mitogen-activated protein (MAP) kinases in arsenite-mediated heme oxygenase-1 gene expression. In LMH cells, sodium arsenite, cadmium, and heat shock, but not heme, induced activity of the MAP kinases extracellular-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. To examine whether these MAP kinases were involved in mediating heme oxygenase-1 gene expression, we utilized constitutively activated and dominant negative components of the ERK, JNK, and p38 MAP kinase signaling pathways. Involvement of an AP-1 site in arsenite induction of heme oxygenase-1 gene expression was studied. We conclude that the MAP kinases ERK and p38 are involved in the induction of heme oxygenase-1, and that at least one AP-1 element (located -1576 base pairs upstream of the transcription start site) is involved in this response.
J Biol Chem. 1998 Apr 10;273(15):8922-31.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/42430
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