TY - JOUR
T1 - Upregulation of oxidative stress gene markers during SARS-COV-2 viral infection
AU - Saheb Sharif-Askari, Narjes
AU - Saheb Sharif-Askari, Fatemeh
AU - Mdkhana, Bushra
AU - Hussain Alsayed, Hawra Ali
AU - Alsafar, Habiba
AU - Alrais, Zeyad Faoor
AU - Hamid, Qutayba
AU - Halwani, Rabih
N1 - Funding Information:
This research has been financially supported by Tissue Injury and Repair (TIR) group operational grant (Grant code: 150317 ); COVID-19 research grant (CoV19-0307), Seed grant (Grant code: 2001090275 ); and by collaborative research grant (Grant code: 2001090278 ) to RH, University of Sharjah, UAE ; and by a Sandooq Al Watan Applied Research & Development grant to RH ( SWARD-S20-007 ), UAE; and by Al Jalila Foundation Seed Grant ( AJF202019 ), UAE; and by Prince Abdullah Ben Khalid Celiac Disease Research Chair , under the Vice Deanship of Research Chairs, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/8/20
Y1 - 2021/8/20
N2 - Severe viral infections, including SARS-COV-2, could trigger disruption of the balance between pro-oxidant and antioxidant mediators; the magnitude of which could reflect the severity of infection and lung injury. Using publicly available COVID-19 transcriptomic datasets, we conducted an in-silico analyses to evaluate the expression levels of 125 oxidative stress genes, including 37 pro-oxidant genes, 32 oxidative-responsive genes, and 56 antioxidant genes. Seven oxidative stress genes were found to be upregulated in whole blood and lung autopsies (MPO, S100A8, S100A9, SRXN1, GCLM, SESN2, and TXN); these genes were higher in severe versus non-severe COVID-19 leucocytes. Oxidative genes were upregulated in inflammatory cells comprising macrophages and CD8+ T cells isolated from bronchioalveolar fluid (BALF), and neutrophils isolated from peripheral blood. MPO, S100A8, and S100A9 were top most upregulated oxidative markers within COVID-19's lung autopsies, whole blood, leucocytes, BALF derived macrophages and circulating neutrophils. The calprotectin's, S100A8 and S100A9 were upregulated in SARS-COV-2 infected human lung epithelium. To validate our in-silico analysis, we conducted qRT-PCR to measure MPO and calprotectin's levels in blood and saliva samples. Relative to uninfected donor controls, MPO, S100A8 and S100A9 were significantly higher in blood and saliva of severe versus asymptomatic COVID-19 patients. Compared to other different viral respiratory infections, coronavirus infection showed a prominent upregulation in oxidative stress genes with MPO and calprotectin at the top of the list. In conclusion, SARS-COV-2 induce the expression of oxidative stress genes via both immune as well as lung structural cells. The observed correlation between oxidative stress genes dysregulation and COVID-19 disease severity deserve more attention. Mechanistical studies are required to confirm the correlation between oxidative stress gene dysregulation, COVID-19 severity, and the net oxidative stress balance.
AB - Severe viral infections, including SARS-COV-2, could trigger disruption of the balance between pro-oxidant and antioxidant mediators; the magnitude of which could reflect the severity of infection and lung injury. Using publicly available COVID-19 transcriptomic datasets, we conducted an in-silico analyses to evaluate the expression levels of 125 oxidative stress genes, including 37 pro-oxidant genes, 32 oxidative-responsive genes, and 56 antioxidant genes. Seven oxidative stress genes were found to be upregulated in whole blood and lung autopsies (MPO, S100A8, S100A9, SRXN1, GCLM, SESN2, and TXN); these genes were higher in severe versus non-severe COVID-19 leucocytes. Oxidative genes were upregulated in inflammatory cells comprising macrophages and CD8+ T cells isolated from bronchioalveolar fluid (BALF), and neutrophils isolated from peripheral blood. MPO, S100A8, and S100A9 were top most upregulated oxidative markers within COVID-19's lung autopsies, whole blood, leucocytes, BALF derived macrophages and circulating neutrophils. The calprotectin's, S100A8 and S100A9 were upregulated in SARS-COV-2 infected human lung epithelium. To validate our in-silico analysis, we conducted qRT-PCR to measure MPO and calprotectin's levels in blood and saliva samples. Relative to uninfected donor controls, MPO, S100A8 and S100A9 were significantly higher in blood and saliva of severe versus asymptomatic COVID-19 patients. Compared to other different viral respiratory infections, coronavirus infection showed a prominent upregulation in oxidative stress genes with MPO and calprotectin at the top of the list. In conclusion, SARS-COV-2 induce the expression of oxidative stress genes via both immune as well as lung structural cells. The observed correlation between oxidative stress genes dysregulation and COVID-19 disease severity deserve more attention. Mechanistical studies are required to confirm the correlation between oxidative stress gene dysregulation, COVID-19 severity, and the net oxidative stress balance.
KW - Antioxidant
KW - Bioinformatics
KW - Calprotectin
KW - COVID-19
KW - Lung autopsies
KW - Myeloperoxidase
KW - Neutrophils
KW - Oxidative stress
KW - Pro-oxidant
KW - Respiratory viral infection
KW - S100A8
KW - S100A9
KW - Saliva
KW - SARS-COV-2
UR - http://www.scopus.com/inward/record.url?scp=85110590609&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2021.06.018
DO - 10.1016/j.freeradbiomed.2021.06.018
M3 - Article
C2 - 34186206
AN - SCOPUS:85110590609
SN - 0891-5849
VL - 172
SP - 688
EP - 698
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
ER -