Adenosine Signaling in Hypoxia Associated Diseases

Presenter: Alejandra Lamas

Research Category: Physical and LIfe Sciences
College: College of Engineering
Major(s): Bioengineering
Graduation Date: 2023

Tissue hypoxia has been recognized to be clinically linked with many pathological conditions and disease states, such as ischemic tissue injury, tumor progression and immunosuppression. Under hypoxia, HIF-1alpha stabilizes and enhances its transcriptional activity. Target genes of HIF-1 regulates cell proliferation, angiogenesis and metabolism in response to hypoxia.

The Gs-coupled Adenosine 2B receptor (A2BR) is excessively activated under hypoxia as well, due to extracellular elevated adenosine levels under hypoxic conditions. Coincidentally, several downstream effectors of A2BR, including PKA and ERK1/2, are also reported to modify HIF-1_ through phosphorylation. PKA specifically phosphorylates Thr(63) and Ser(692) on HIF-1_ and enhances HIF transcriptional activity and target gene expression.

To determine the effects of A2BR stimulation/inhibition on HIF-1alpha, we will overexpress A2BR in human embryonic kidney (HEK) cells and treat them with either agonist or antagonist under hypoxia and then measure HIF-1alpha accumulation levels and phosphorylation of HIF-1alpha using immuno-precipitation and Western blots.