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Revisiting the Effects of Xenon on Urate Oxidase and Tissue Plasminogen Activator: No Evidence for Inhibition by Noble Gases
Frontiers in Molecular Biosciences ( IF 3.9 ) Pub Date : 2020-08-14 , DOI: 10.3389/fmolb.2020.574477
Jesse Cahill , Anne M. Ruffing

Although chemically inert, Xe and other noble gases have been shown to have functional effects on biological systems. For example, Xe is a powerful anesthetic with neuroprotective properties. Recent reports have claimed that Xe inhibits the activity of tissue plasminogen activator (tPA) and urate oxidase (UOX), indicating that the use of Xe as an anesthetic may have undesirable side effects. Here, we revisited the methods used to demonstrate Xe inhibition of UOX and tPA, testing both indirect and direct gas delivery methods with variable bubble sizes and gas flowrates. Our results indicate that Xe or Kr do not affect the activity of UOX or tPA and that the previously reported inhibition is due to protein damage attendant to directly bubbling gases into protein solutions. The lack of evidence to support Xe inhibition of UOX or tPA alleviates concerns regarding possible side effects for the clinical application of Xe as an anesthetic. Furthermore, this study illustrates the importance of using indirect methods of gas dissolution for studying gas-protein interactions in aqueous solution.



中文翻译:

再次探讨氙对尿酸氧化酶和组织纤溶酶原激活物的影响:没有证据表明稀有气体会抑制这种气体

尽管Xe和其他稀有气体具有化学惰性,但已证明对生物系统具有功能作用。例如,Xe是一种具有神经保护特性的强大麻醉剂。最近的报道声称Xe抑制组织纤溶酶原激活剂(tPA)和尿酸氧化酶(UOX)的活性,表明使用Xe作为麻醉剂可能会产生不良副作用。在这里,我们重新介绍了用于证明Xe抑制UOX和tPA的方法,测试了具有可变气泡大小和气体流速的间接和直接气体输送方法。我们的结果表明,Xe或Kr不会影响UOX或tPA的活性,并且先前报道的抑制作用是由于直接将气体鼓泡进入蛋白质溶液而引起的蛋白质破坏。缺乏支持Xe抑制UOX或tPA的证据,减轻了对Xe作为麻醉剂临床应用的可能副作用的担忧。此外,这项研究说明了使用间接气体溶解方法研究水溶液中气体-蛋白质相互作用的重要性。

更新日期:2020-09-11
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