HIF-1 alpha - sensing and responding to changing oxygen levels

Thu, 04/30/2015 - 14:53

Hypoxia-inducible factor 1 (HIF-1) allows cells to respond to changing levels of oxygen in the environment. HIF-1 is a heterodimeric transcription factor consisting of alpha and beta subunits. Under normal conditions HIF-1 alpha is continuously synthesized and degraded. HIF-1 alpha degradation is mediated through an oxygen-dependent degradation domain that is hydroxylated and leads to ubiquitylation and proteolysis. HIF-1 beta on the other hand is constitutively expressed and localizes to the nucleus. Under hypoxic conditions HIF-1alpha is stabilized and translocates to the nucleus where it dimerizes with HIF-1 beta. There it binds to hypoxia response elements (HRE) in the promoters of target genes involved in angiogenesis and cell proliferation including vascular endothelial growth factor (VEGF) and erythropoietin.  HIF-1 alpha also helps regulate cell metabolism under hypoxic conditions by controlling the expression of members of the glycolytic pathway. HIF-1 alpha represents a potential target in cancer therapies to inhibit tumor progression by limiting the supply of oxygen and nutrients.

Colegio et al. published an article in Nature detailing the role of lactic acid in the interaction between macrophages and growing tumors (1). They demonstrated lactic acid generated by tumors is able to activate HIF-1alpha in neighboring macrophages leading to VEGF induction and growth and maintenance of the tumor. The used the HIF-1 alpha antibody to monitor cell responses to either hypoxic conditions or to tumor-conditioned media. HIF-1α stability can also be manipulated in order to alleviate the effects of ischemic stroke. Reischl et al. used drugs inhibiting the hydroxylation and degradation of HIF-1alpha to activate a hypoxic response and improve outcomes following stroke (2). The HIF-1 alpha antibody allowed them to monitor HIF-1alpha levels and stability following drug treatment. The Yuan group from Harvard examined potential health risks associated with low-dose radiation exposure (3). They used the HIF-1 alpha antibody for immunofluorescence to show radiation exposure induces HIF-1 alpha expression and causes a shift in cell metabolism from oxidative phosphorlyation to aerobic glycolysis. In a separate study the same group showed HIF-1alpha induction by low dose arsenic treatment can selectively provide radiation resistance to normal cells during radiotherapy cancer treatment (4). They used the HIF-1 alpha antibody to monitor HIF-1 alpha levels using immunofluorescence. They demonstrated HIF-1 alpha induction requires functional p53 and increases cellular resistance to radiation, providing a strategy to selectively protect normal cells. The Simon group shared their research in Nature on the role of fructose-1, 6-bisphosphatase 1 (FBP1) in kidney cancer (5). They performed immunoprecipitation experiments using the HIF-1 alpha antibody to look at the direct interaction of FBP1 and HIF-1 alpha. FBP1 depletion in cancer cells prevents the inhibition of HIF-1 alpha and allows cancer cells to alter their metabolism to grow and proliferate.

Novus Biologicals offers HIF-1 alpha reagents for your research needs including:


  1. 25043024
  2. 24409307
  3. 24583639
  4. 24391088
  5. 25043030

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