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Differential regulation of HIF‐1 alpha and VEGF in an anoxia tolerant brain
Author(s) -
Milton Sarah L,
Kesaraju Shailaja,
Ayyanathan Kasirajan,
Prentice Howard
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1022.1
Subject(s) - biology , vascular endothelial growth factor , downregulation and upregulation , hypoxia (environmental) , endocrinology , medicine , microbiology and biotechnology , chemistry , vegf receptors , biochemistry , oxygen , cancer research , gene , organic chemistry
We examined vascular endothelial growth factor (VEGF) expression during anoxia and related it to the binding activity and expression of HIF‐1alpha in the anoxia tolerant turtle Trachemys scripta . Whole animals and neuronal cultures were exposed to anoxia and reoxygenation to determine changes in mRNA and protein levels; immunohistochemistry showed VEGF in brain slices while EMSA was performed for HIF binding. High constitutive VEGF transcript and protein levels increased 2‐fold during anoxia, returning to basal upon reoxygenation. Brain slice VEGF‐positive cells also increased following 24h anoxia; VEGF colabelled with NeuN in the cortex while ependymal cells were positive for VEGF only. By contrast, high basal HIF protein levels did not increase in anoxia or reoxygenation, and decreased in whole brain nuclear extracts, as did DNA binding activity. As the results suggested a suppression of HIF in anoxia, we exposed cells to a HIF stimulator, which significantly increased cell death over 4h anoxia. Thus while VEGF is upregulated in this anoxia tolerant model, it is unlikely to be regulated by HIF. As HIF binding in hypoxic conditions promotes many functions known to be actively downregulated in the anoxic turtle, it is not surprising that nuclear levels and HIF binding decrease in this model, to the point where increased HIF activity decreases cell survival. This work was funded by NIH grant R15 S048909–01 to SLM.