School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, Louisiana.
J Biochem Mol Toxicol. 2019 Oct;33(10):e22380. doi: 10.1002/jbt.22380. Epub 2019 Jul 24.
Lung endothelial barrier dysfunction leads to severe pathologies, including the lethal Acute Respiratory Distress Syndrome. P53 has been associated with anti-inflammatory activities. The current study employs a variety of unfolded protein response (UPR) activators and inhibitors to investigate the regulation of P53 by UPR in lung cells. The bovine cells that were exposed to the UPR inductors brefeldin A, dithiothreitol, and thapsigargin; demonstrated elevated expression levels of P53 compared to the vehicle-treated cells. On the contrary, the UPR inhibitors N-acetyl cysteine, kifunensine, and ATP-competitive IRE1α kinase-inhibiting RNase attenuator; produced the opposite effects. The outcomes of the present study reveal a positive regulation between UPR and P53. Since it has been shown that a mild induction of the unfolded protein response opposes inflammation, we suggest that P53 is involved in those protective activities in the lung.
肺内皮屏障功能障碍可导致严重的病理变化，包括致命的急性呼吸窘迫综合征。P53 与抗炎活性有关。本研究采用多种未折叠蛋白反应 (UPR) 激活剂和抑制剂来研究 UPR 对肺细胞中 P53 的调节。与用载体处理的细胞相比，牛细胞暴露于 UPR 诱导剂布雷菲德菌素 A、二硫苏糖醇和 thapsigargin 后，P53 的表达水平升高。相反，UPR 抑制剂 N-乙酰半胱氨酸、衣霉素和 ATP 竞争型 IRE1α 激酶抑制性核糖核酸酶衰减子产生了相反的效果。本研究的结果揭示了 UPR 和 P53 之间的正调节。由于已经表明轻度诱导未折叠蛋白反应可以对抗炎症，因此我们认为 P53 参与了肺中的这些保护活动。
