SARS-CoV-2 N protein interacts with SLC7A11 to cause ferroptosis in acute lung injury
Main Article Content
Keywords
SARS-CoV-2, N protein, acute lung injury, ferroptosis, SLC7A11
Abstract
Background: The nucleocapsid protein (N protein) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is elevated in bodily fluids at the onset of infection and has recently been found to have a direct role in lung damage. However, the exact mode of action of the N protein in acute lung injury is still unknown.
Method: Recombinant N protein was used to treat mice and A549 cells in vivo and in vitro. Enzyme-linked immunosorbent assay and hematoxylin and eosin staining were used to detect the levels of inflammatory factors and lung damage in lung tissue. The total iron and Fe2+ contents and the expression of ferroptosis markers in mouse lung tissues and cells were detected. Co-immunoprecipitation detects the binding of N protein and solute carrier family 7 member 11 (SLC7A11). Replenishment experiments were conducted by activating SLC7A11 to study the effect of SLC7A11 on N protein–induced lung injury.
Result: Recombinant N protein caused acute lung injury and lung inflammation, increased total iron and Fe2+ contents in vivo and in vitro, promoted the expression of ACSL4, inhibited the expression of GPX4 and FTH1, and triggered ferroptosis. Recombinant N protein can interact with SLC7A11, and activating SLC7A11 can reverse N protein–induced ferroptosis and acute lung injury.
Conclusion: SARS-CoV-2 N protein can directly interact with SLC7A11 to cause ferroptosis, which produces a lot of inflammatory factors and results in lung injury in mice.
References
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