Regulation of hyperoxia-induced neonatal lung injury via post-translational cysteine redox modifications.
Regulation of hyperoxia-induced neonatal lung injury via post-translational cysteine redox modifications.
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DOI：
10.1016/j.redox.2022.102405
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发表时间：
2022-09
期刊：
影响因子：
11.4
通讯作者：
Helms, My N.
中科院分区：
文献类型：
--
作者：
Zhang, Tong;Day, Nicholas J.;Gaffrey, Matthew;Weitz, Karl K.;Attah, Kwame;Mimche, Patrice N.;Paine, Robert, III;Qian, Wei-Jun;Helms, My N.
早产儿和肺部疾病患者的肺部通常有过多的液体，经常用氧气治疗，但长期暴露于高氧会导致不可逆的肺损伤。虽然高氧的不良反应是由活性氧介导的，但高氧对肺中氧化还原依赖性调节的影响程度尚不清楚。在这项研究中，新生小鼠过度表达上皮钠通道（β-ENaC）的β-亚基编码的Scnn 1b和野生型（WT; C57 B16）的同窝仔，研究高分数吸入氧（FiO 2）诱导的肺损伤的发病机制。结果表明，在转基因Scnn 1b小鼠O2诱导的肺损伤是减弱慢性O2暴露。为了验证蛋白质可逆的半胱氨酸氧化还原修饰在O2诱导的肺损伤中发挥重要作用的假设，我们对WT和Scnn 1b过表达小鼠从出生到出生后11-15天在21%O2（常氧）或FiO 2 85%（高氧）下进行了蛋白质组范围的蛋白S-谷胱甘肽化（SSG）分析。超过7700个独特的半胱氨酸位点与SSG修饰的鉴定和定量，涵盖了3000多个蛋白质在肺。在这两种小鼠模型中，高氧导致属于不同范围的蛋白质的Cys位点的SSG水平的显著改变。此外，大量的SSG变化中观察到Scnn 1b过表达的小鼠暴露于高氧，这表明ENaC在细胞调节中起着至关重要的作用。高氧诱导的SSG变化进一步得到巯基总氧化（蛋白半胱氨酸残基可逆氧化的总体水平）观察结果的支持。差异分析表明，Scnn 1b过表达可能通过调节细胞粘附、血液凝固和蛋白水解等特定过程来防止高氧诱导的肺损伤。这项研究提供了肺中蛋白质氧化的全景图，并强调了氧化还原调节在O2诱导的肺损伤中的重要性。新生小鼠肺内scnn 1b过表达减轻高氧肺损伤。在高氧诱导的肺损伤中发现的新分子和生物学过程。揭示了SCNN 1B在高氧下的保护作用的潜在机制。
Preterm infants and patients with lung disease often have excess fluid in the lungs and are frequently treated with oxygen, however long-term exposure to hyperoxia results in irreversible lung injury. Although the adverse effects of hyperoxia are mediated by reactive oxygen species, the full extent of the impact of hyperoxia on redox-dependent regulation in the lung is unclear. In this study, neonatal mice overexpressing the beta-subunit of the epithelial sodium channel (β-ENaC) encoded by Scnn1b and their wild type (WT; C57Bl6) littermates were utilized to study the pathogenesis of high fraction inspired oxygen (FiO2)-induced lung injury. Results showed that O2-induced lung injury in transgenic Scnn1b mice is attenuated following chronic O2 exposure. To test the hypothesis that reversible cysteine-redox-modifications of proteins play an important role in O2-induced lung injury, we performed proteome-wide profiling of protein S-glutathionylation (SSG) in both WT and Scnn1b overexpressing mice maintained at 21% O2 (normoxia) or FiO2 85% (hyperoxia) from birth to 11–15 days postnatal. Over 7700 unique Cys sites with SSG modifications were identified and quantified, covering more than 3000 proteins in the lung. In both mouse models, hyperoxia resulted in a significant alteration of the SSG levels of Cys sites belonging to a diverse range of proteins. In addition, substantial SSG changes were observed in the Scnn1b overexpressing mice exposed to hyperoxia, suggesting that ENaC plays a critically important role in cellular regulation. Hyperoxia-induced SSG changes were further supported by the results observed for thiol total oxidation, the overall level of reversible oxidation on protein cysteine residues. Differential analyses reveal that Scnn1b overexpression may protect against hyperoxia-induced lung injury via modulation of specific processes such as cell adhesion, blood coagulation, and proteolysis. This study provides a landscape view of protein oxidation in the lung and highlights the importance of redox regulation in O2-induced lung injury. Scnn1b overexpression in neonatal mouse lung attenuated hyperoxia induced lung injury. Novel molecules and biological processes identified in hyperoxia-induced lung injury. Potential mechanisms revealed for SCNN1B protective effect under hyperoxia.
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DOI：
10.1152/ajplung.00359.2014
发表时间：
2015-09-01
影响因子：
4.9
作者：
Bouch, Sheena;O'Reilly, Megan;Sozo, Foula
通讯作者：
Sozo, Foula
DOI：
10.3791/62671
发表时间：
2021-06-21
期刊：
Journal of visualized experiments : JoVE
影响因子：
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作者：
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通讯作者：
Qian WJ
影响因子：
8.8
作者：
Berry, Kayla N.;Brett, Tom J.
通讯作者：
Brett, Tom J.
影响因子：
17.1
作者：
Duan J;Kodali VK;Gaffrey MJ;Guo J;Chu RK;Camp DG;Smith RD;Thrall BD;Qian WJ
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Qian WJ
DOI：
10.1152/ajplung.00260.2011
发表时间：
2012-02-01
影响因子：
4.9
作者：
Goodson, Preston;Kumar, Amrita;Helms, My N.
通讯作者：
Helms, My N.