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Calcineurin Activates Cytoglobin Transcription in Hypoxic Myocytes
- Source :
- Journal of Biological Chemistry. 284:10409-10421
- Publication Year :
- 2009
- Publisher :
- Elsevier BV, 2009.
-
Abstract
- Cardiac hypertrophy develops in response to a variety of cardiovascular stresses and results in activation of numerous signaling cascades and proteins. In the present study, we demonstrate that cytoglobin is a stress-responsive hemoprotein in the hypoxia-induced hypertrophic myocardium and it is transcriptionally regulated by calcineurin-dependent transcription factors. The cytoglobin transcript level is abundantly expressed in the adult heart and in response to hypoxia cytoglobin expression is markedly up-regulated within the hypoxia-induced hypertrophic heart. To define the molecular mechanism resulting in the induction of cytoglobin, we undertook a transcriptional analysis of the 5′ upstream regulatory region of the cytoglobin gene. Evolutionarily conserved binding elements for transcription factors HIF-1, AP-1, and NFAT are located within the upstream region of the cytoglobin gene. Transcriptional assays demonstrated that calcineurin activity modulates cytoglobin transcription. Increased calcineurin activity enhances the ability of NFAT and AP-1 to bind to the putative cytoglobin promoter, especially under hypoxic conditions. In addition, inhibition of calcineurin, NFAT, and/or AP-1 activities decreases endogenous cytoglobin transcript and protein levels. Thus, the regulation of cytoglobin transcription by calcineurin-dependent transcription factors suggests that cytoglobin may have a functional role in calcium-dependent events accompanying cardiac remodeling.
- Subjects :
- Male
Transcriptional Activation
Transgene
Mice, Transgenic
Biology
Response Elements
Biochemistry
Cell Line
Mice
Transcription (biology)
Animals
Humans
Transcription, Chromatin, and Epigenetics
Myocytes, Cardiac
Globin
Hypoxia
Promoter Regions, Genetic
Molecular Biology
Transcription factor
Gene
Base Sequence
Calcineurin
Cytoglobin
JNK Mitogen-Activated Protein Kinases
NFAT
Cell Biology
Molecular biology
Globins
Rats
Mice, Inbred C57BL
Mutagenesis, Site-Directed
Hypertrophy, Left Ventricular
Proto-Oncogene Proteins c-fos
Sequence Alignment
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 284
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....8bc6387a5b83f78b433771d19f39d56a
- Full Text :
- https://doi.org/10.1074/jbc.m809572200