Selenoprotein V (SELENOV) contains a thioredoxin-like fold and a conserved CxxU motif with a potential redox function. This study was to assess its in vivo and in vitro roles and mechanisms in coping with different oxidant insults. In Experiment (Expt.)1, SELENOV knockout (KO) and wild type (WT) mice (male, 8-wk old) were given an ip injection of saline, diquat (DQ, 12.5 mg/kg), or N-acetyl-para-aminophenol (APAP, 300 mg/kg) (n = 10), and killed 5 h after the injection. In Expt. 2, primary hepatocytes of WT and KO were treated with DQ (0-0.75 mM) or APAP (0-6 mM) for 12 h. In Expt. 3, 293 T cells overexpressing Selenov gene (OE) were treated with APAP (0-4 mM) for 24 h or H₂O₂ (0-0.4 mM) for 12 h. Compared with the WT, the DQ- and APAP-injected KO mice had higher (P < 0.05) serum alanine aminotransferase activities and hepatic malondialdehyde (MDA), protein carbonyl, endoplasmic reticulum (ER) stress-related proteins (BIP and CHOP), apoptosis-related proteins (FAK and caspase-9), and 3-nitrotyrosine, along with lower total anti-oxidizing-capability (T-AOC) and severer hepatic necrosis. Likewise, the DQ and APAP-treated KO hepatocytes had elevated (P < 0.05) cell death (10-40%), decreased (P < 0.05) T-AOC (63-83%), glutathione (26-87%), superoxide dismutase (SOD) activity (28-36%), mRNA levels of redox enzymes (Cat, Gcs, Gpx3, and Sod) and (or) sharper declines (P < 0.05) in cellular respiration and ATP production than that of the WT cells. In contrast, the OE cells had greater viability and T-AOC and lower MDA, and carbonyl contents after the APAP and H₂O₂ exposures (all at P < 0.05) than the controls. Moreover, the OE cells had greater (P < 0.05) redox enzyme activities (GPX, TrxR, and SOD), and lower (P < 0.05) expressions of ER stress-related genes (Atf4, Atf6, Bip, Xbp1t, Xbp1s, and Chop) and proteins (BIP, CHOP, FAK, and caspase-9) than the control cells after the treatment of H₂O₂ (0.4 mM). In conclusion, SELENOV conferred protections in vivo and in vitro against the reactive oxygen and nitrogen species-mediated ER stress-related signaling and oxidative injuries.

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