SARS-CoV-2 spike glycoprotein increases oxidative stress in SH-SY5Y cells. (a) H2O2 emissions in digitonin-permeabilized SH-SY5Y cells was higher in SH-Spike cells (n = 11 SH-EV, n = 12 SH-Spike). (b) Immunoblotting of antioxidant enzymes, SOD1 or SOD2, revealed no differences. SARS-CoV-2 spike glycoprotein expression in SH-SY5Y cells decreased GPX4 protein expression (n = 9). (c) Total glutathione and reduced glutathione concentrations were lower in SH-Spike cells compared to SH-EV (n = 8 SH-EV, n = 9 SH-Spike). (d) Protein carbonyls did not differ between SH-Spike and SH-EV cells (n = 9). Comparisons between groups were determined using a two-tailed Student's t-test. Values are mean ± SD. *P < 0.05, **P < 0.01, ***P < 0.001.