Effect of ATM inhibition in primary endothelial cells

Analysis of gene expresssion in HUVECs following ATM inhibition. The main objective of the study was to get insights about the metabolic pathways regulated by ATM in primary endothelial cells.Here we demonstrate that besides the DNA damage repair defect, metabolic dysregulation causes several of the phenotypes observed in AT patients. We discovered a new aspect of metabolic control by ATM, the control of cystine and arginine influx via the phosphorylation of CD98HC. Our data provide further insights into why NAC treatment and production of GSH is beneficial to AT patients aside from antioxidant effects and we propose a novel mechanistic link between these acute responses and disease manifestation. Overall design: Total RNA-seq was performed in two different isolates of HUVECs and each condition run in triplicates. HUVECs were between passages 3-5. Cells were treated with either the drug delivery vehicle (DMSO) or ATM inhibitors (5uM KU60019 or 10uM KU55933) for 8 hours.