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PLoS One. 2015 Apr 1;10(4):e0123649. doi: 10.1371/journal.pone.0123649. eCollection 2015.

Dose-dependent effects of allopurinol on human foreskin fibroblast cells and human umbilical vein endothelial cells under hypoxia.

Author information

1
Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, United Kingdom.
2
Division of Medical Sciences, Ninewells Hospital and Medical School, Dundee, United Kingdom.

Abstract

Allopurinol, an inhibitor of xanthine oxidase, has been used in clinical trials of patients with cardiovascular and chronic kidney disease. These are two pathologies with extensive links to hypoxia and activation of the transcription factor hypoxia inducible factor (HIF) family. Here we analysed the effects of allopurinol treatment in two different cellular models, and their response to hypoxia. We explored the dose-dependent effect of allopurinol on Human Foreskin Fibroblasts (HFF) and Human Umbilical Vein Endothelial Cells (HUVEC) under hypoxia and normoxia. Under normoxia and hypoxia, high dose allopurinol reduced the accumulation of HIF-1α protein in HFF and HUVEC cells. Allopurinol had only marginal effects on HIF-1α mRNA level in both cellular systems. Interestingly, allopurinol effects over the HIF system were independent of prolyl-hydroxylase activity. Finally, allopurinol treatment reduced angiogenesis traits in HUVEC cells in an in vitro model. Taken together these results indicate that high doses of allopurinol inhibits the HIF system and pro-angiogenic traits in cells.

PMID:
25830774
PMCID:
PMC4382188
DOI:
10.1371/journal.pone.0123649
[Indexed for MEDLINE]
Free PMC Article

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