Respiratory Diseases Group, Respiratory Service, La Paz University Hospital, IdiPAZ, 28029 Madrid, Spain.
Biomedical Research Networking Center on Respiratory Diseases (CIBERES), 28029 Madrid, Spain.
Biomolecules. 2022 Mar 13;12(3):442. doi: 10.3390/biom12030442.
Severe COVID-19 disease leads to hypoxemia, inflammation and lymphopenia. Viral infection induces cellular stress and causes the activation of the innate immune response. The ubiquitin-proteasome system (UPS) is highly implicated in viral immune response regulation. The main function of the proteasome is protein degradation in its active form, which recognises and binds to ubiquitylated proteins. Some proteasome subunits have been reported to be upregulated under hypoxic and hyperinflammatory conditions. Here, we conducted a prospective cohort study of COVID-19 patients ( = 44) and age-and sex-matched controls ( = 20). In this study, we suggested that hypoxia could induce the overexpression of certain genes encoding for subunits from the α and β core of the 20S proteasome and from regulatory particles (19S and 11S) in COVID-19 patients. Furthermore, the gene expression of proteasome subunits was associated with lymphocyte count reduction and positively correlated with inflammatory molecular and clinical markers. Given the importance of the proteasome in maintaining cellular homeostasis, including the regulation of the apoptotic and pyroptotic pathways, these results provide a potential link between COVID-19 complications and proteasome gene expression.
严重的 COVID-19 疾病会导致低氧血症、炎症和淋巴细胞减少。病毒感染会诱导细胞应激，导致先天免疫反应的激活。泛素-蛋白酶体系统（UPS）在病毒免疫反应调节中起着重要作用。蛋白酶体的主要功能是以其活性形式降解蛋白质，它可以识别并结合泛素化的蛋白质。已经有报道称，某些蛋白酶体亚基在低氧和炎症反应过度的情况下会被上调。在这里，我们对 COVID-19 患者（=44）和年龄及性别匹配的对照组（=20）进行了一项前瞻性队列研究。在这项研究中，我们提出，缺氧可能会诱导 COVID-19 患者 20S 蛋白酶体的α和β核心以及调节颗粒（19S 和 11S）中某些编码亚基的基因过度表达。此外，蛋白酶体亚基的基因表达与淋巴细胞计数减少有关，并与炎症分子和临床标志物呈正相关。鉴于蛋白酶体在维持细胞内稳态方面的重要性，包括对细胞凋亡和焦亡途径的调节，这些结果为 COVID-19 并发症与蛋白酶体基因表达之间的潜在联系提供了依据。
