Molecular and Cellular Biochemistry

, Volume 436, Issue 1–2, pp 23–28 | Cite as

Suppression of phosphorylated MAPK and caspase 3 by carbon dioxide

  • Yan-Jun Xu
  • Vijayan Elimban
  • Naranjan S. Dhalla


Although CO2 is produced during the oxidation of different substrates in all types of cells, the role of this gas in the regulation of cellular function is not clearly understood. Since changes in several signal transduction as well as apoptotic, anti-apoptotic, and other proteins are known to modify cellular function, we investigated if some of these proteins are altered upon incubating the rat hind leg skeletal muscle in a medium enriched with CO2 (1000–1200 ppm) for 30 min. CO2 was observed to depress phosphorylated levels of ERK1 (P44) and ERK2 (P42) without affecting the unphosphorylated content of these MAPK proteins. On the other hand, no change in p38 MAPK protein was found but the content of its degradation product 30 kDa proteins (both phosphorylated and unphosphorylated) was decreased. No alterations in the content of other signaling proteins (PKA and Akt), inflammatory molecule (TNF-α), and vascular endothelial growth factor (VEGF) were seen upon exposure of the muscle to CO2. The content for apoptotic and anti-apoptotic proteins (Bad and Bcl2), except for a decrease in caspase 3, were also not affected by CO2. These results indicate that CO2 may serve as a gasotransmitter to regulate cellular function by depressing MAPK and caspase 3 activities.


Signal transduction proteins Apoptotic and anti-apoptotic proteins Inflammatory molecule Growth factors 



The infrastructure support for this study was provided by the St. Boniface Hospital Research Foundation, Winnipeg, Canada.

Compliance with ethical standards

Conflict of interest

This is to declare that the research was funded by Mitsubishi Rayon Cleansui Co., Ltd., Tokyo, Japan and that Y.-J. Xu, V. Elimban and N.S. Dhalla had no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Yan-Jun Xu
    • 1
    • 2
  • Vijayan Elimban
    • 1
    • 2
  • Naranjan S. Dhalla
    • 1
    • 2
  1. 1.Institute of Cardiovascular SciencesSt. Boniface Hospital Albrechtsen Research CentreWinnipegCanada
  2. 2.Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health SciencesUniversity of ManitobaWinnipegCanada

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