| First Author | Yun JW | Year | 2013 |
| Journal | Free Radic Biol Med | Volume | 65 |
| Pages | 291-300 | PubMed ID | 23811004 |
| Mgi Jnum | J:329216 | Mgi Id | MGI:6872099 |
| Doi | 10.1016/j.freeradbiomed.2013.06.034 | Citation | Yun JW, et al. (2013) A novel upregulation of glutathione peroxidase 1 by knockout of liver-regenerating protein Reg3beta aggravates acetaminophen-induced hepatic protein nitration. Free Radic Biol Med 65:291-300 |
| abstractText | Murine regenerating islet-derived 3beta (Reg3beta) represents a homologue of human hepatocarcinoma-intestine-pancreas/pancreatic-associated protein and enhances mouse susceptibility to acetaminophen (APAP)-induced hepatotoxicity. Our objective was to determine if and how knockout of Reg3beta (KO) affects APAP (300 mg/kg, ip)-mediated protein nitration in mouse liver. APAP injection produced greater levels of hepatic protein nitration in the KO than in the wild-type mice. Their elevated protein nitration was alleviated by a prior injection of recombinant mouse Reg3beta protein and was associated with an accelerated depletion of the peroxynitrite (ONOO(-)) scavenger glutathione by an upregulated hepatic glutathione peroxidase-1 (GPX1) activity. The enhanced GPX1 production in the KO mice was mediated by an 85% rise (p<0.05) in the activity of selenocysteine lyase (Scly), a key enzyme that mobilizes Se for selenoprotein biosynthesis. Knockout of Reg3beta enhanced AP-1 protein and its binding activity to the Scly gene promoter, upregulating its gene transcription. However, knockout of Reg3beta did not affect gene expression of other key factors for selenoprotein biosynthesis. In conclusion, our findings unveil a new metabolic role for Reg3beta in protein nitration and a new biosynthesis control of GPX1 by a completely "unrelated" regenerating protein, Reg3beta, via transcriptional activation of Scly in coping with hepatic protein nitration. Linking selenoproteins to tissue regeneration will have profound implications in understanding the mechanism of Se functions and physiological coordination of tissue regeneration with intracellular redox control. |
