Bax inhibitor-1 (BI-1) is an anti-apoptotic protein located in the endoplasmic reticulum (ER). The role of BI-1 has been studied in different physiopathological models including ischemia, diabetes, liver regeneration and cancer. However, fundamental knowledge about the effects of BI-1 deletion on the proteome is lacking. To further explore this protein, we compared the levels of different proteins in bi-1-/- and bi-1+/+ mouse tissues by two-dimensional electrophoresis (2-DE) and mass spectrometry (MS). In several bi-1-/- mice, glucose-regulated protein 75 (GRP75/mortalin/ PBP74/mthsp70), peroxiredoxin6 (Prx6) and fumarylacetoacetate hydrolase (FAH) showed a pI shift that could be attributed to post-translational modifications. Selenium-binding protein 2 (SBP2) and ferritin light chain 1 levels were significantly increased. Phosphatidylethanolamine-binding protein-1 (PEBP-1) was dramatically decreased in bi-1-/- mice, which was confirmed by Western blotting. The phosphorylation of GRP75, Prx6 and FAH were compared between bi-1+/+ and bi-1-/- mice using liver tissue lysates. Of these three proteins, only one exhibited modified phosphorylation; Tyr phosphorylation of Prx6 was increased in bi-1-/- mice. Our protein profiling results provide fundamental knowledge about the physiopathological function of BI-1.

Keywords: 2-DE, Bax inhibitor-1, ER stress, MS, proteomics