School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, LA, 71201, USA.
Department of Clinical Endocrinology, Medical University of Lodz, Poland.
Immunobiology. 2019 Jul;224(4):532-538. doi: 10.1016/j.imbio.2019.04.008. Epub 2019 Apr 18.
The tumor suppressor protein P53 is strongly involved in orchestrating cellular defenses in the diverse variety of human tissues. Anomalies to lung endothelium permeability are streaming severe consequences towards human health, often associated with fatal outcomes. Ongoing investigations suggest that P53 exerts a prominent strategic role in crucial signaling cascades, in charge of both the maintenance and defense of pulmonary endothelium against toxic intruders. The current study employs human and bovine lung microvascular cells, as well as pharmacologic and genetic P53 modulators to demonstrate the negative regulation of APE1/Ref1 by P53. Moreover, it includes real time measurements of endothelial permeability, to reveal the disruptive role of APE1/Ref1 towards endothelial integrity. Those findings supports our efforts to elucidate the highly sophisticated regulatory network that enact endothelial adaptations under the plethora of challenging environmental factors.
肿瘤抑制蛋白 P53 强烈参与调控人体组织中多样化的细胞防御机制。肺内皮通透性异常会对人类健康产生严重后果，常伴有致命结局。目前的研究采用人源和牛源肺微血管细胞以及药理学和遗传学 P53 调节剂，证明 P53 对 APE1/Ref1 具有负调控作用。此外，还进行了内皮通透性的实时测量，以揭示 APE1/Ref1 对内皮完整性的破坏作用。这些发现支持了我们阐明在众多挑战性环境因素下内皮适应性的高度复杂调控网络的努力。
