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Induction of carbonic anhydrase IX by hypoxia and chemical disruption of oxygen sensing in rat fibroblasts and cardiomyocytes

  • Cell and Molecular Physiology
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Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

CA IX is an active transmembrane carbonic anhydrase isoform functionally implicated in cell adhesion and pH control. Human CA IX is strongly induced by hypoxia and frequently associated with various tumors. In this study, we investigated the expression of the rat CA IX in response to chronic hypoxia and to treatment with chemical compounds that disrupt oxygen sensing, including dimethyloxalylglycine, dimethylester succinate, diazoxide, and tempol. We brought the evidence that expression of CA IX is regulated by hypoxia and hypoxia-mimicking compounds in immortalized Rat2 fibroblasts and BP6 rat fibrosarcoma cells in a cell-type-specific manner. We also demonstrated, for the first time, that CA IX is expressed in hypoxic primary rat cardiomyocytes and in immortalized H9c2 cardiomyocytes exposed to physiological or chemical hypoxia and that CA IX expression is increased in hypoxic rat tissues in vivo. Our findings suggest that CA IX expression is not limited to cancer but may be also induced in other pathological situations associated with ischemia or metabolic disturbances leading to activation of the HIF pathway. These data support the view that rats can represent useful model for studies of CA IX as a component of endogenous protection mechanisms associated with hypoxia or perturbed oxygen sensing.

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Abbreviations

CA IX:

carbonic anhydrase IX protein

CA9 :

human carbonic anhydrase 9 gene

Car9 :

rodent carbonic anhydrase 9 gene

DMOG:

dimethyloxalylglycine

DMS:

dimethylester succinate

DZO:

diazoxide

GLUT-1:

glucose transporter 1

GLUT-4:

glucose transporter 4

HIF:

hypoxia-inducible factor

MCT4:

monocarboxylate transporter 4

iNOS:

inducible nitric oxide synthase

N-TAD:

N-terminal transactivation domain

ODDD:

oxygen-dependent degradation domain

PHD:

prolyl hydroxylase

ROS:

radical oxygen species

TL:

tempol

VEGF:

vascular endothelial growth factor

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Acknowledgement

This work was supported by grants from EU (6FP Integrated project EUROXY, LSCH-CT-2003-502932), from Research and Development Support Agency (Contracts APVV-51-024805 and APVV-51-027404), and from VEGA (2/7126/27).

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Authors and Affiliations

  1. Institute of Virology, Centre of Excellence in Cardiovascular Research, Slovak Academy of Sciences, Dubravska cesta 9, 845 05, Bratislava, Slovak Republic

    Tereza Holotnakova, Anna Ohradanova, Alzbeta Hulikova, Juraj Kopacek, Jaromir Pastorek & Silvia Pastorekova

  2. Institute for Heart Research, Centre of Excellence in Cardiovascular Research, Slovak Academy of Sciences, Bratislava, Slovak Republic

    Attila Ziegelhoffer

  3. Department of Physiology, Medical Faculty of Masaryk University, Brno, Czech Republic

    Marie Novakova

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  1. Tereza Holotnakova
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  2. Attila Ziegelhoffer
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  3. Anna Ohradanova
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Correspondence to Silvia Pastorekova.

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Holotnakova, T., Ziegelhoffer, A., Ohradanova, A. et al. Induction of carbonic anhydrase IX by hypoxia and chemical disruption of oxygen sensing in rat fibroblasts and cardiomyocytes. Pflugers Arch - Eur J Physiol 456, 323–337 (2008). https://doi.org/10.1007/s00424-007-0400-6

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  • DOI: https://doi.org/10.1007/s00424-007-0400-6

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