Paradoxical effects of hypoxia-mimicking divalent cobalt ions in human endothelial cells in vitro

Kirsten Peters; Harald Schmidt; Ronald E. Unger; Günter Kamp; Felicitas Pröls; Bernhard J. Berger; C. James Kirkpatrick

doi:10.1007/s11010-005-4504-z

Paradoxical effects of hypoxia-mimicking divalent cobalt ions in human endothelial cells in vitro

Kirsten Peters, Harald Schmidt, Ronald E. Unger, Günter Kamp, Felicitas Pröls, Bernhard J. Berger, C. James Kirkpatrick

Research output: Contribution to journal › Article › peer-review

54 Scopus citations

Abstract

Divalent cobalt ions (Co²⁺) induce the expression of hypoxia responsive genes and are often used in cell biology to mimic hypoxia. In this in vitro Co²⁺ on human endothelial cells and examined processes that are stimulated in hypoxia in vivo (proliferation and angiogenesis). We analyzed the expression of the hypoxia-inducible factor-1α (HIF-1α) under different hypoxic conditions (3% and nearly 0% O₂) and Co²⁺-concentrations (0.01-0.7 mM). As in hypoxia, the amount of HIF-1α protein was enhanced by exposure to Co²⁺ (did not correlate with mRNA amount). However, contrary to the results of hypoxia, in vitro-angiogenesis was inhibited after exposure to even low Co²⁺-concentrations (≥0.01 mM). This led to the conclusion that although hypoxia signaling after Co²⁺-exposure took place, further yet unknown Co²⁺-induced event(s) must have occurred.

Original language	English
Pages (from-to)	157-166
Number of pages	10
Journal	Molecular and Cellular Biochemistry
Volume	270
Issue number	1-2
DOIs	https://doi.org/10.1007/s11010-005-4504-z
State	Published - Feb 2005
Externally published	Yes

Bibliographical note

Funding Information:
This work was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft) Priority Program “Biosystem”. We want to thank Susanne Barth, Sabine Aust, and Anne Sartoris for their excellent technical assistance and the Knoll AG, Ludwigshafen (Germany) for the generous gift of ArvinTM.

Funding

This work was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft) Priority Program “Biosystem”. We want to thank Susanne Barth, Sabine Aust, and Anne Sartoris for their excellent technical assistance and the Knoll AG, Ludwigshafen (Germany) for the generous gift of ArvinTM.

Funders	Funder number
Deutsche Forschungsgemeinschaft

Keywords

Angiogenesis
Cobalt
Endothelial cells
Hypoxia
Hypoxia inducible factor-17α
in vitro

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10.1007/s11010-005-4504-z

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abstract = "Divalent cobalt ions (Co2+) induce the expression of hypoxia responsive genes and are often used in cell biology to mimic hypoxia. In this in vitro Co2+ on human endothelial cells and examined processes that are stimulated in hypoxia in vivo (proliferation and angiogenesis). We analyzed the expression of the hypoxia-inducible factor-1α (HIF-1α) under different hypoxic conditions (3% and nearly 0% O2) and Co2+-concentrations (0.01-0.7 mM). As in hypoxia, the amount of HIF-1α protein was enhanced by exposure to Co2+ (did not correlate with mRNA amount). However, contrary to the results of hypoxia, in vitro-angiogenesis was inhibited after exposure to even low Co2+-concentrations (≥0.01 mM). This led to the conclusion that although hypoxia signaling after Co2+-exposure took place, further yet unknown Co2+-induced event(s) must have occurred.",

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note = "Funding Information: This work was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft) Priority Program “Biosystem”. We want to thank Susanne Barth, Sabine Aust, and Anne Sartoris for their excellent technical assistance and the Knoll AG, Ludwigshafen (Germany) for the generous gift of ArvinTM.",

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AU - Pröls, Felicitas

AU - Berger, Bernhard J.

AU - Kirkpatrick, C. James

N1 - Funding Information: This work was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft) Priority Program “Biosystem”. We want to thank Susanne Barth, Sabine Aust, and Anne Sartoris for their excellent technical assistance and the Knoll AG, Ludwigshafen (Germany) for the generous gift of ArvinTM.

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N2 - Divalent cobalt ions (Co2+) induce the expression of hypoxia responsive genes and are often used in cell biology to mimic hypoxia. In this in vitro Co2+ on human endothelial cells and examined processes that are stimulated in hypoxia in vivo (proliferation and angiogenesis). We analyzed the expression of the hypoxia-inducible factor-1α (HIF-1α) under different hypoxic conditions (3% and nearly 0% O2) and Co2+-concentrations (0.01-0.7 mM). As in hypoxia, the amount of HIF-1α protein was enhanced by exposure to Co2+ (did not correlate with mRNA amount). However, contrary to the results of hypoxia, in vitro-angiogenesis was inhibited after exposure to even low Co2+-concentrations (≥0.01 mM). This led to the conclusion that although hypoxia signaling after Co2+-exposure took place, further yet unknown Co2+-induced event(s) must have occurred.

AB - Divalent cobalt ions (Co2+) induce the expression of hypoxia responsive genes and are often used in cell biology to mimic hypoxia. In this in vitro Co2+ on human endothelial cells and examined processes that are stimulated in hypoxia in vivo (proliferation and angiogenesis). We analyzed the expression of the hypoxia-inducible factor-1α (HIF-1α) under different hypoxic conditions (3% and nearly 0% O2) and Co2+-concentrations (0.01-0.7 mM). As in hypoxia, the amount of HIF-1α protein was enhanced by exposure to Co2+ (did not correlate with mRNA amount). However, contrary to the results of hypoxia, in vitro-angiogenesis was inhibited after exposure to even low Co2+-concentrations (≥0.01 mM). This led to the conclusion that although hypoxia signaling after Co2+-exposure took place, further yet unknown Co2+-induced event(s) must have occurred.

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Paradoxical effects of hypoxia-mimicking divalent cobalt ions in human endothelial cells in vitro

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