Article

Cobalt induces hypoxia-inducible factor-1alpha expression in airway smooth muscle cells by a reactive oxygen species- and PI3K-dependent mechanism.

Laboratory of Physiology, Department of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.
American Journal of Respiratory Cell and Molecular Biology (impact factor: 5.13). 12/2004; 31(5):544-51. DOI:10.1165/rcmb.2003-0426OC pp.544-51
Source: PubMed

ABSTRACT Cobalt can mimic hypoxia and has been implicated as a cause of lung defects. However, the effect of cobalt on airway smooth muscle (ASM) cells has not been analyzed in detail. In this article, we use primary cultures of ASM cells from rabbit trachea and show that exposure to cobalt chloride causes a rapid increase of the intracellular levels of hypoxia-inducible factor-1alpha, which is detected predominantly inside the nucleus. With the use of specific inhibitors, we demonstrate that induction of hypoxia-inducible factor-1alpha by cobalt depends on active protein synthesis but not transcription. Furthermore, wortmannin, LY294002, and N-acetyl-L-cysteine inhibit the effect of cobalt, suggesting that it involves the phosphatidylinositol 3 kinase pathway and production of reactive oxygen species. Interestingly, cobalt chloride attenuates the contractile response of rabbit airways induced by potassium chloride, but not by acetylcholine, suggesting a link between the cellular response to hypoxic stimuli and the contractile properties of ASM cells.

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Keywords

acetylcholine
 
active protein synthesis
 
airway smooth muscle
 
cellular response
 
cobalt
 
cobalt chloride causes
 
contractile properties
 
contractile response
 
hypoxia-inducible factor-1alpha
 
induction
 
intracellular levels
 
N-acetyl-L-cysteine
 
phosphatidylinositol 3 kinase pathway
 
potassium chloride
 
rabbit airways induced
 
reactive oxygen species
 
specific inhibitors