{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:57:03Z","timestamp":1790783823159,"version":"4.1.0"},"reference-count":95,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T00:00:00Z","timestamp":1647129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/01612"],"award-info":[{"award-number":["PI19\/01612"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["COV20\/00207"],"award-info":[{"award-number":["COV20\/00207"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CP18\/00028"],"award-info":[{"award-number":["CP18\/00028"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19-01363"],"award-info":[{"award-number":["PI19-01363"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>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 (n = 44) and age-and sex-matched controls (n = 20). In this study, we suggested that hypoxia could induce the overexpression of certain genes encoding for subunits from the \u03b1 and \u03b2 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.<\/jats:p>","DOI":"10.3390\/biom12030442","type":"journal-article","created":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T22:29:43Z","timestamp":1647210583000},"page":"442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Upregulated Proteasome Subunits in COVID-19 Patients: A Link with Hypoxemia, Lymphopenia and Inflammation"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4681-147X","authenticated-orcid":false,"given":"Enrique","family":"Alfaro","sequence":"first","affiliation":[{"name":"Respiratory Diseases Group, Respiratory Service, La Paz University Hospital, IdiPAZ, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4549-0678","authenticated-orcid":false,"given":"Elena","family":"D\u00edaz-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Respiratory Diseases Group, Respiratory Service, La Paz University Hospital, IdiPAZ, 28029 Madrid, Spain"},{"name":"Biomedical Research Networking Center on Respiratory Diseases (CIBERES), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Garc\u00eda-Tovar","sequence":"additional","affiliation":[{"name":"Respiratory Diseases Group, Respiratory Service, La Paz University Hospital, IdiPAZ, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6053-7844","authenticated-orcid":false,"given":"Ester","family":"Zamarr\u00f3n","sequence":"additional","affiliation":[{"name":"Respiratory Diseases Group, Respiratory Service, La Paz University Hospital, IdiPAZ, 28029 Madrid, Spain"},{"name":"Biomedical Research Networking Center on Respiratory Diseases (CIBERES), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Mangas","sequence":"additional","affiliation":[{"name":"Respiratory Diseases Group, Respiratory Service, La Paz University Hospital, IdiPAZ, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra\u00fal","family":"Galera","sequence":"additional","affiliation":[{"name":"Respiratory Diseases Group, Respiratory Service, La Paz University Hospital, IdiPAZ, 28029 Madrid, Spain"},{"name":"Biomedical Research Networking Center on Respiratory Diseases (CIBERES), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"L\u00f3pez-Collazo","sequence":"additional","affiliation":[{"name":"Innate Immune Response Group, IdiPAZ, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7227-2238","authenticated-orcid":false,"given":"Francisco","family":"Garc\u00eda-Rio","sequence":"additional","affiliation":[{"name":"Respiratory Diseases Group, Respiratory Service, La Paz University Hospital, IdiPAZ, 28029 Madrid, Spain"},{"name":"Biomedical Research Networking Center on Respiratory Diseases (CIBERES), 28029 Madrid, Spain"},{"name":"Faculty of Medicine, Autonomous University of Madrid, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1948-4514","authenticated-orcid":false,"given":"Carolina","family":"Cubillos-Zapata","sequence":"additional","affiliation":[{"name":"Respiratory Diseases Group, Respiratory Service, La Paz University Hospital, IdiPAZ, 28029 Madrid, Spain"},{"name":"Biomedical Research Networking Center on Respiratory Diseases (CIBERES), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.immuni.2020.05.002","article-title":"Immunology of COVID-19: Current State of the Science","volume":"52","author":"Vabret","year":"2020","journal-title":"Immunity"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e12967","DOI":"10.1111\/sji.12967","article-title":"Lymphopenia an important immunological abnormality in patients with COVID-19: Possible mechanisms","volume":"93","author":"Jafarzadeh","year":"2021","journal-title":"Scand. 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