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Calcineurin Activates Cytoglobin Transcription in Hypoxic Myocytes

Authors :
Pradeep P.A. Mammen
Daniel J. Garry
Michael J. Birrer
Sarvjeet Singh
Devanjan Sikder
Shilpa M. Manda
Beverly A. Rothermel
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.

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