دورية أكاديمية

Effect of SARS-CoV-2 S protein on the proteolytic cleavage of the epithelial Na+ channel ENaC.

التفاصيل البيبلوغرافية
العنوان: Effect of SARS-CoV-2 S protein on the proteolytic cleavage of the epithelial Na+ channel ENaC.
المؤلفون: Magaña-Ávila, Germán Ricardo, Moreno, Erika, Plata, Consuelo, Carbajal-Contreras, Héctor, Murillo-de-Ozores, Adrian Rafael, García-Ávila, Kevin, Vázquez, Norma, Syed, Maria, Wysocki, Jan, Batlle, Daniel, Gamba, Gerardo, Castañeda-Bueno, María
المصدر: PLoS ONE; 4/25/2024, Vol. 19 Issue 4, p1-14, 14p
مصطلحات موضوعية: SODIUM channels, ADULT respiratory distress syndrome, SARS-CoV-2, ION channels
مستخلص: Severe cases of COVID-19 are characterized by development of acute respiratory distress syndrome (ARDS). Water accumulation in the lungs is thought to occur as consequence of an exaggerated inflammatory response. A possible mechanism could involve decreased activity of the epithelial Na+ channel, ENaC, expressed in type II pneumocytes. Reduced transepithelial Na+ reabsorption could contribute to lung edema due to reduced alveolar fluid clearance. This hypothesis is based on the observation of the presence of a novel furin cleavage site in the S protein of SARS-CoV-2 that is identical to the furin cleavage site present in the alpha subunit of ENaC. Proteolytic processing of αENaC by furin-like proteases is essential for channel activity. Thus, competition between S protein and αENaC for furin-mediated cleavage in SARS-CoV-2-infected cells may negatively affect channel activity. Here we present experimental evidence showing that coexpression of the S protein with ENaC in a cellular model reduces channel activity. In addition, we show that bidirectional competition for cleavage by furin-like proteases occurs between 〈ENaC and S protein. In transgenic mice sensitive to lethal SARS-CoV-2, however, a significant decrease in gamma ENaC expression was not observed by immunostaining of lungs infected as shown by SARS-CoV2 nucleoprotein staining. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:19326203
DOI:10.1371/journal.pone.0302436