Is Low Alveolar Type II Cell SOD3 in the Lungs of Elderly Linked to the Observed Severity of COVID-19?
Identifieur interne : 000405 ( Main/Exploration ); précédent : 000404; suivant : 000406Is Low Alveolar Type II Cell SOD3 in the Lungs of Elderly Linked to the Observed Severity of COVID-19?
Auteurs : Ahmed S. Abouhashem [États-Unis] ; Kanhaiya Singh [États-Unis] ; Hassan Me Azzazy [États-Unis] ; Chandan K. Sen [États-Unis]Source :
- Antioxidants & redox signaling [ 1557-7716 ] ; 2020.
Abstract
Human lungs single cell RNA sequencing data from healthy donors (elderly and young; GEO accession number GSE122960) were analyzed to isolate and specifically study gene expression in alveolar type II cells. Co-localization of ACE2 and TMPRSS2 enables SARS-CoV 2 to enter the cells. Expression of these genes in the alveolar type II cells of elderly and young patients were comparable and therefore do not seem to be responsible for worse outcomes observed in COVID-19 affected elderly. In cells from the elderly, 263 genes were downregulated and 95 upregulated. SOD3 was identified as the top-ranked gene that was most down-regulated in the elderly. Other redox-active genes that were also downregulated in cells from the elderly included ATF4 and M2TA. ATF4, an ER stress sensor that defends lungs via induction of heme oxygenase 1. The study of downstream factors known to be induced by ATF4, according to Ingenuity Pathway AnalysisTM, identified 24 candidates. Twenty-one of these were significantly downregulated in the cells from the elderly. These downregulated candidates were subjected to enrichment using the Reactome Database identifying that in the elderly, the ability to respond to heme deficiency and the ATF4-dependent ability to respond to endoplasmic reticulum stress is significantly compromised. SOD3-based therapeutic strategies have provided beneficial results in treating lung disorders including fibrosis. The findings of this work propose the hypotheses that lung-specific delivery of SOD3/ATF4 related antioxidants may work in synergy with promising anti-viral drugs such as remdesivir to further improve COVID-19 outcomes in the elderly.
DOI: 10.1089/ars.2020.8111
PubMed: 32323565
Affiliations:
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Abouhashem</name><affiliation wicri:level="2"><nlm:affiliation>Indiana University School of Medicine, 12250, Surgery, Indianapolis, Indiana, United States; aabouhas@iu.edu.</nlm:affiliation><country wicri:rule="url">États-Unis</country><wicri:regionArea>Indiana University School of Medicine, 12250, Surgery, Indianapolis, Indiana</wicri:regionArea><placeName><region type="state">Indiana</region></placeName></affiliation></author><author><name sortKey="Singh, Kanhaiya" sort="Singh, Kanhaiya" uniqKey="Singh K" first="Kanhaiya" last="Singh">Kanhaiya Singh</name><affiliation wicri:level="1"><nlm:affiliation>Indiana University School of Medicine, 12250, Surgery, IB 444, 975 West Walnut Street, Indianapolis, Indiana, United States, 46202; kanh@iu.edu.</nlm:affiliation><country wicri:rule="url">États-Unis</country><wicri:regionArea>Indiana University School of Medicine, 12250, Surgery, IB 444, 975 West Walnut Street, Indianapolis, Indiana, United States</wicri:regionArea><wicri:noRegion>United States</wicri:noRegion></affiliation></author><author><name sortKey="Azzazy, Hassan Me" sort="Azzazy, Hassan Me" uniqKey="Azzazy H" first="Hassan Me" last="Azzazy">Hassan Me Azzazy</name><affiliation wicri:level="1"><nlm:affiliation>The American University in Cairo, 11341, Department of Chemistry, School of Sciences & Engineering, New Cairo, Cairo, Egypt; hazzazy@aucegypt.edu.</nlm:affiliation><country wicri:rule="url">États-Unis</country><wicri:regionArea>The American University in Cairo, 11341, Department of Chemistry, School of Sciences & Engineering, New Cairo, Cairo</wicri:regionArea><wicri:noRegion>Cairo</wicri:noRegion></affiliation></author><author><name sortKey="Sen, Chandan K" sort="Sen, Chandan K" uniqKey="Sen C" first="Chandan K" last="Sen">Chandan K. Sen</name><affiliation wicri:level="1"><nlm:affiliation>Indiana University School of Medicine, 12250, Surgery, MRLB Suite 454, 975 W Walnut Street, Indianapolis, Indiana, United States, 46202-5114; cksen@iu.edu.</nlm:affiliation><country wicri:rule="url">États-Unis</country><wicri:regionArea>Indiana University School of Medicine, 12250, Surgery, MRLB Suite 454, 975 W Walnut Street, Indianapolis, Indiana, United States</wicri:regionArea><wicri:noRegion>United States</wicri:noRegion></affiliation></author></analytic><series><title level="j">Antioxidants & redox signaling</title><idno type="eISSN">1557-7716</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Human lungs single cell RNA sequencing data from healthy donors (elderly and young; GEO accession number GSE122960) were analyzed to isolate and specifically study gene expression in alveolar type II cells. Co-localization of ACE2 and TMPRSS2 enables SARS-CoV 2 to enter the cells. Expression of these genes in the alveolar type II cells of elderly and young patients were comparable and therefore do not seem to be responsible for worse outcomes observed in COVID-19 affected elderly. In cells from the elderly, 263 genes were downregulated and 95 upregulated. SOD3 was identified as the top-ranked gene that was most down-regulated in the elderly. Other redox-active genes that were also downregulated in cells from the elderly included ATF4 and M2TA. ATF4, an ER stress sensor that defends lungs via induction of heme oxygenase 1. The study of downstream factors known to be induced by ATF4, according to Ingenuity Pathway AnalysisTM, identified 24 candidates. Twenty-one of these were significantly downregulated in the cells from the elderly. These downregulated candidates were subjected to enrichment using the Reactome Database identifying that in the elderly, the ability to respond to heme deficiency and the ATF4-dependent ability to respond to endoplasmic reticulum stress is significantly compromised. SOD3-based therapeutic strategies have provided beneficial results in treating lung disorders including fibrosis. The findings of this work propose the hypotheses that lung-specific delivery of SOD3/ATF4 related antioxidants may work in synergy with promising anti-viral drugs such as remdesivir to further improve COVID-19 outcomes in the elderly.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Indiana</li></region></list><tree><country name="États-Unis"><region name="Indiana"><name sortKey="Abouhashem, Ahmed S" sort="Abouhashem, Ahmed S" uniqKey="Abouhashem A" first="Ahmed S" last="Abouhashem">Ahmed S. Abouhashem</name></region><name sortKey="Azzazy, Hassan Me" sort="Azzazy, Hassan Me" uniqKey="Azzazy H" first="Hassan Me" last="Azzazy">Hassan Me Azzazy</name><name sortKey="Sen, Chandan K" sort="Sen, Chandan K" uniqKey="Sen C" first="Chandan K" last="Sen">Chandan K. Sen</name><name sortKey="Singh, Kanhaiya" sort="Singh, Kanhaiya" uniqKey="Singh K" first="Kanhaiya" last="Singh">Kanhaiya Singh</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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