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  • The spike protein of SARS-CoV-2 induces heme oxygenase-1: Pathophysiologic implications #MMPMID34920080
  • Singh RD; Barry MA; Croatt AJ; Ackerman AW; Grande JP; Diaz RM; Vile RG; Agarwal A; Nath KA
  • Biochim Biophys Acta Mol Basis Dis 2022[Mar]; 1868 (3): 166322 PMID34920080show ga
  • BACKGROUND: Acute kidney injury (AKI) is both a consequence and determinant of outcomes in COVID-19. The kidney is one of the major organs infected by the causative virus, SARS-CoV-2. Viral entry into cells requires the viral spike protein, and both the virus and its spike protein appear in the urine of COVID-19 patients with AKI. We examined the effects of transfecting the viral spike protein of SARS-CoV-2 in kidney cell lines. METHODS: HEK293, HEK293-ACE2(+) (stably overexpressing ACE2), and Vero E6 cells having endogenous ACE2 were transfected with SARS-CoV-2 spike or control plasmid. Assessment of gene and protein expression, and syncytia formation was performed, and the effects of quercetin on syncytia formation examined. FINDINGS: Spike transfection in HEK293-ACE2(+) cells caused syncytia formation, cellular sloughing, and focal denudation of the cell monolayer; transfection in Vero E6 cells also caused syncytia formation. Spike expression upregulated potentially nephrotoxic genes (TNF-alpha, MCP-1, and ICAM1). Spike upregulated the cytoprotective gene HO-1 and relevant signaling pathways (p-Akt, p-STAT3, and p-p38). Quercetin, an HO-1 inducer, reduced syncytia formation and spike protein expression. INTERPRETATION: The major conclusions of the study are: 1) Spike protein expression in kidney cells provides a relevant model for the study of maladaptive and adaptive responses germane to AKI in COVID-19; 2) such spike protein expression upregulates HO-1; and 3) quercetin, an HO-1 inducer, may provide a clinically relevant/feasible protective strategy in AKI occurring in the setting of COVID-19. FUNDING: R01-DK119167 (KAN), R01-AI100911 (JPG), P30-DK079337; R01-DK059600 (AA).
  • |Animals[MESH]
  • |COVID-19/*metabolism/virology[MESH]
  • |Cell Line[MESH]
  • |Chlorocebus aethiops[MESH]
  • |HEK293 Cells[MESH]
  • |Heme Oxygenase-1/*metabolism[MESH]
  • |Host-Pathogen Interactions/drug effects/physiology[MESH]
  • |Humans[MESH]
  • |Protein Binding/drug effects/physiology[MESH]
  • |Quercetin/pharmacology[MESH]
  • |SARS-CoV-2/*pathogenicity[MESH]
  • |Signal Transduction/drug effects/physiology[MESH]
  • |Spike Glycoprotein, Coronavirus/*metabolism[MESH]
  • |Up-Regulation/drug effects/physiology[MESH]
  • |Vero Cells[MESH]
  • |Virus Internalization/drug effects[MESH]

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  • suck abstract from ncbi

    166322 3.1868 2022