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Evidence of Structural Protein Damage and Membrane Lipid Remodeling in Red Blood Cells from COVID-19 Patients.
J Proteome Res. 2020 11 06; 19(11):4455-4469.JP

Abstract

The SARS-CoV-2 beta coronavirus is the etiological driver of COVID-19 disease, which is primarily characterized by shortness of breath, persistent dry cough, and fever. Because they transport oxygen, red blood cells (RBCs) may play a role in the severity of hypoxemia in COVID-19 patients. The present study combines state-of-the-art metabolomics, proteomics, and lipidomics approaches to investigate the impact of COVID-19 on RBCs from 23 healthy subjects and 29 molecularly diagnosed COVID-19 patients. RBCs from COVID-19 patients had increased levels of glycolytic intermediates, accompanied by oxidation and fragmentation of ankyrin, spectrin beta, and the N-terminal cytosolic domain of band 3 (AE1). Significantly altered lipid metabolism was also observed, in particular, short- and medium-chain saturated fatty acids, acyl-carnitines, and sphingolipids. Nonetheless, there were no alterations of clinical hematological parameters, such as RBC count, hematocrit, or mean corpuscular hemoglobin concentration, with only minor increases in mean corpuscular volume. Taken together, these results suggest a significant impact of SARS-CoV-2 infection on RBC structural membrane homeostasis at the protein and lipid levels. Increases in RBC glycolytic metabolites are consistent with a theoretically improved capacity of hemoglobin to off-load oxygen as a function of allosteric modulation by high-energy phosphate compounds, perhaps to counteract COVID-19-induced hypoxia. Conversely, because the N-terminus of AE1 stabilizes deoxyhemoglobin and finely tunes oxygen off-loading and metabolic rewiring toward the hexose monophosphate shunt, RBCs from COVID-19 patients may be less capable of responding to environmental variations in hemoglobin oxygen saturation/oxidant stress when traveling from the lungs to peripheral capillaries and vice versa.

Authors+Show Affiliations

Department of Pathology & Cell Biology, Columbia University, New York, New York 10032, United States.Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado 80045, United States.Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado 80045, United States.Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado 80045, United States.Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado 80045, United States.Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado 80045, United States.Department of Pathology & Cell Biology, Columbia University, New York, New York 10032, United States.Department of Pathology & Cell Biology, Columbia University, New York, New York 10032, United States.Department of Pathology, University of Maryland, Baltimore, Maryland 21201, United States.Department of Pathology, University of Virginia, Charlottesville, Virginia 22903, United States.Department of Pathology & Cell Biology, Columbia University, New York, New York 10032, United States.Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado 80045, United States.Department of Pathology & Cell Biology, Columbia University, New York, New York 10032, United States.Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado 80045, United States.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

33103907

Citation

Thomas, Tiffany, et al. "Evidence of Structural Protein Damage and Membrane Lipid Remodeling in Red Blood Cells From COVID-19 Patients." Journal of Proteome Research, vol. 19, no. 11, 2020, pp. 4455-4469.
Thomas T, Stefanoni D, Dzieciatkowska M, et al. Evidence of Structural Protein Damage and Membrane Lipid Remodeling in Red Blood Cells from COVID-19 Patients. J Proteome Res. 2020;19(11):4455-4469.
Thomas, T., Stefanoni, D., Dzieciatkowska, M., Issaian, A., Nemkov, T., Hill, R. C., Francis, R. O., Hudson, K. E., Buehler, P. W., Zimring, J. C., Hod, E. A., Hansen, K. C., Spitalnik, S. L., & D'Alessandro, A. (2020). Evidence of Structural Protein Damage and Membrane Lipid Remodeling in Red Blood Cells from COVID-19 Patients. Journal of Proteome Research, 19(11), 4455-4469. https://doi.org/10.1021/acs.jproteome.0c00606
Thomas T, et al. Evidence of Structural Protein Damage and Membrane Lipid Remodeling in Red Blood Cells From COVID-19 Patients. J Proteome Res. 2020 11 6;19(11):4455-4469. PubMed PMID: 33103907.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence of Structural Protein Damage and Membrane Lipid Remodeling in Red Blood Cells from COVID-19 Patients. AU - Thomas,Tiffany, AU - Stefanoni,Davide, AU - Dzieciatkowska,Monika, AU - Issaian,Aaron, AU - Nemkov,Travis, AU - Hill,Ryan C, AU - Francis,Richard O, AU - Hudson,Krystalyn E, AU - Buehler,Paul W, AU - Zimring,James C, AU - Hod,Eldad A, AU - Hansen,Kirk C, AU - Spitalnik,Steven L, AU - D'Alessandro,Angelo, Y1 - 2020/10/26/ PY - 2020/10/27/pubmed PY - 2020/10/27/medline PY - 2020/10/26/entrez KW - AE1 KW - SARS-CoV-2 KW - band 3 KW - erythrocyte KW - lipidomics KW - metabolomics KW - proteomics SP - 4455 EP - 4469 JF - Journal of proteome research JO - J Proteome Res VL - 19 IS - 11 N2 - The SARS-CoV-2 beta coronavirus is the etiological driver of COVID-19 disease, which is primarily characterized by shortness of breath, persistent dry cough, and fever. Because they transport oxygen, red blood cells (RBCs) may play a role in the severity of hypoxemia in COVID-19 patients. The present study combines state-of-the-art metabolomics, proteomics, and lipidomics approaches to investigate the impact of COVID-19 on RBCs from 23 healthy subjects and 29 molecularly diagnosed COVID-19 patients. RBCs from COVID-19 patients had increased levels of glycolytic intermediates, accompanied by oxidation and fragmentation of ankyrin, spectrin beta, and the N-terminal cytosolic domain of band 3 (AE1). Significantly altered lipid metabolism was also observed, in particular, short- and medium-chain saturated fatty acids, acyl-carnitines, and sphingolipids. Nonetheless, there were no alterations of clinical hematological parameters, such as RBC count, hematocrit, or mean corpuscular hemoglobin concentration, with only minor increases in mean corpuscular volume. Taken together, these results suggest a significant impact of SARS-CoV-2 infection on RBC structural membrane homeostasis at the protein and lipid levels. Increases in RBC glycolytic metabolites are consistent with a theoretically improved capacity of hemoglobin to off-load oxygen as a function of allosteric modulation by high-energy phosphate compounds, perhaps to counteract COVID-19-induced hypoxia. Conversely, because the N-terminus of AE1 stabilizes deoxyhemoglobin and finely tunes oxygen off-loading and metabolic rewiring toward the hexose monophosphate shunt, RBCs from COVID-19 patients may be less capable of responding to environmental variations in hemoglobin oxygen saturation/oxidant stress when traveling from the lungs to peripheral capillaries and vice versa. SN - 1535-3907 UR - https://www.unboundmedicine.com/medline/citation/33103907/Evidence_of_Structural_Protein_Damage_and_Membrane_Lipid_Remodeling_in_Red_Blood_Cells_from_COVID-19_Patients L2 - https://doi.org/10.1021/acs.jproteome.0c00606 DB - PRIME DP - Unbound Medicine ER -
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