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Hypoxia reprograms calcium signaling and regulates myoglobin expression.

Publication ,  Journal Article
Kanatous, SB; Mammen, PPA; Rosenberg, PB; Martin, CM; White, MD; Dimaio, JM; Huang, G; Muallem, S; Garry, DJ
Published in: Am J Physiol Cell Physiol
March 2009

Myoglobin is an oxygen storage molecule that is selectively expressed in cardiac and slow-twitch skeletal muscles that have a high oxygen demand. Numerous studies have implicated hypoxia in the regulation of myoglobin expression as an adaptive response to hypoxic stress. However, the details of this relationship remain undefined. In the present study, adult mice exposed to 10% oxygen for periods up to 3 wk exhibited increased myoglobin expression only in the working heart, whereas myoglobin was either diminished or unchanged in skeletal muscle groups. In vitro and in vivo studies revealed that hypoxia in the presence or absence of exercise-induced stimuli reprograms calcium signaling and modulates myoglobin gene expression. Hypoxia alone significantly altered calcium influx in response to cell depolarization or depletion of endoplasmic reticulum calcium stores, which inhibited the expression of myoglobin. In contrast, our whole animal and transcriptional studies indicate that hypoxia in combination with exercise enhanced the release of calcium from the sarcoplasmic reticulum via the ryanodine receptors triggered by caffeine, which increased the translocation of nuclear factor of activated T-cells into the nucleus to transcriptionally activate myoglobin expression. The present study unveils a previously unrecognized mechanism where the hypoxia-mediated regulation of calcium transients from different intracellular pools modulates myoglobin gene expression. In addition, we observed that changes in myoglobin expression, in response to hypoxia, are not dependent on hypoxia-inducible factor-1 or changes in skeletal muscle fiber type. These studies enhance our understanding of hypoxia-mediated gene regulation and will have broad applications for the treatment of myopathic diseases.

Duke Scholars

Published In

Am J Physiol Cell Physiol

DOI

ISSN

0363-6143

Publication Date

March 2009

Volume

296

Issue

3

Start / End Page

C393 / C402

Location

United States

Related Subject Headings

  • Up-Regulation
  • Transfection
  • Transcriptional Activation
  • Time Factors
  • Sarcoplasmic Reticulum
  • Ryanodine Receptor Calcium Release Channel
  • Promoter Regions, Genetic
  • Physiology
  • NFATC Transcription Factors
  • Myoglobin
 

Citation

APA
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MLA
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Kanatous, S. B., Mammen, P. P. A., Rosenberg, P. B., Martin, C. M., White, M. D., Dimaio, J. M., … Garry, D. J. (2009). Hypoxia reprograms calcium signaling and regulates myoglobin expression. Am J Physiol Cell Physiol, 296(3), C393–C402. https://doi.org/10.1152/ajpcell.00428.2008
Kanatous, Shane B., Pradeep P. A. Mammen, Paul B. Rosenberg, Cindy M. Martin, Michael D. White, J Michael Dimaio, Guojin Huang, Shmuel Muallem, and Daniel J. Garry. “Hypoxia reprograms calcium signaling and regulates myoglobin expression.Am J Physiol Cell Physiol 296, no. 3 (March 2009): C393–402. https://doi.org/10.1152/ajpcell.00428.2008.
Kanatous SB, Mammen PPA, Rosenberg PB, Martin CM, White MD, Dimaio JM, et al. Hypoxia reprograms calcium signaling and regulates myoglobin expression. Am J Physiol Cell Physiol. 2009 Mar;296(3):C393–402.
Kanatous, Shane B., et al. “Hypoxia reprograms calcium signaling and regulates myoglobin expression.Am J Physiol Cell Physiol, vol. 296, no. 3, Mar. 2009, pp. C393–402. Pubmed, doi:10.1152/ajpcell.00428.2008.
Kanatous SB, Mammen PPA, Rosenberg PB, Martin CM, White MD, Dimaio JM, Huang G, Muallem S, Garry DJ. Hypoxia reprograms calcium signaling and regulates myoglobin expression. Am J Physiol Cell Physiol. 2009 Mar;296(3):C393–C402.

Published In

Am J Physiol Cell Physiol

DOI

ISSN

0363-6143

Publication Date

March 2009

Volume

296

Issue

3

Start / End Page

C393 / C402

Location

United States

Related Subject Headings

  • Up-Regulation
  • Transfection
  • Transcriptional Activation
  • Time Factors
  • Sarcoplasmic Reticulum
  • Ryanodine Receptor Calcium Release Channel
  • Promoter Regions, Genetic
  • Physiology
  • NFATC Transcription Factors
  • Myoglobin