Pig α₁-Acid Glycoprotein: Characterization and First Description in Any Species as a Negative Acute Phase Protein.

The serum protein α1-acid glycoprotein (AGP), also known as orosomucoid, is generally described as an archetypical positive acute phase protein. Here, porcine AGP was identified, purified and characterized from pooled pig serum. It was found to circulate as a single chain glycoprotein having an apparent molecular weight of 43 kDa by SDS-PAGE under reducing conditions, of which approximately 17 kDa were accounted for by N-bound oligosaccharides. Those data correspond well with the properties of the protein predicted from the single porcine AGP gene (ORM1, Q29014 (UniProt)), containing 5 putative glycosylation sites. A monoclonal antibody (MAb) was produced and shown to quantitatively and specifically react with all microheterogenous forms of pig AGP as analyzed by 2-D electrophoresis. This MAb was used to develop an immunoassay (ELISA) for quantification of AGP in pig serum samples. The adult serum concentrations of pig AGP were in the range of 1-3 mg/ml in a number of conventional pig breeds while it was lower in Göttingen and Ossabaw minipigs (in the 0.3 to 0.6 mg/ml range) and higher in young (2-5 days old) conventional pigs (mean: 6.6 mg/ml). Surprisingly, pig AGP was found to behave as a negative acute phase protein during a range of experimental infections and aseptic inflammation with significant decreases in serum concentration and in hepatic ORM1 expression during the acute phase response. To our knowledge this is the first description in any species of AGP being a negative acute phase protein

Mouse models for Glutathione Peroxidase 4 (GPx4).

The selenoperoxidase glutathione peroxidase 4 (GPx4 – also frequently referred to as phospholipid hydroperoxide glutathione peroxidase, PHGPx) is one of the eight glutathione peroxidases in mammals, but the only one known to be essential for early mouse development. GPx4 is emerging as one of the most central selenoproteins, and thus has attracted considerable interest in recent years. Key insights into GPx4 function came from the numerous transgenic and knockout mouse studies performed mainly during the last couple of years, which are summarized here. These investigations not only firmly established a crucial role for GPx4 in male fertility and neuroprotection, but also indicated a major regulatory role of GPx4 in oxidative stress-induced cell death signaling. Beyond this, lipid hydroperoxides (LOOH), downstream of GPx4 inactivation, have been recently shown to control receptor tyrosine kinase (RTK) signaling, thus adding a new layer of complexity to the multifaceted roles of GPx4 in cell signaling and disease development