Gene expression profiling with hypoxia and BRD-K34222889 from primary human pulmonary artery endothelial cells (HPAECs)

BRD-K34222889 is a structural analog of the anti-inflammatory and senolytic drug piperlongumine. Piperlongumine inhibits GSTP1, an enzyme that places glutathione moieties on cysteine residues of various protein targets and for modulation of protein stability. The objective of this experiment was to determine the effect of a Piperlongumine analog BRD-K34222889 in endothelial dysfunction. Interestingly, BRD-K34222889 was found to inhibit glutathione S-transferase P (GSTP1), which increased ISCU protein stability via preventing glutathionylation and thus increased oxidative metabolism and decreased PAEC apoptosis. Activites of BRD-K34222889 reversed gene transcripts altered in PAECs with hypoxia that more than half of these genes were categorized in pathways relevant to cell cycle, cell death, and metabolism and all known to be controlled by ISCU. We use Affymetrix Clairom S platform to determine the whole gene expression. HPAECs were induced with hypoxia with or without BRD-K34222889 and appropriate control for 48h. There were three biological replicate for each group for a total of 9 samples. The groups were Normoxia with vehicle, hypoxia with vehicle, hypoxia with BRD-K34222889