Cloning and expression analysis of chicken phospholipid-hydroperoxide glutathione peroxidase

Phospholipid-hydroperoxide glutathione peroxidase (GPX4 or PHGPX) is a unique selenium dependent glutathione peroxidase that reduces phospholipid, cholesterol, and cholesteryl ester hydroperoxides. Phospholipid-hydroperoxide glutathione peroxidase has been shown to exist as both a 197 amino acid mitochondrial targeting protein and as a 170 amino acid non-mitochondrial protein. The cDNA encoding the non-mitochondrial chicken GPX4 (cGPX4) has been isolated from an immortalized DF-1 chicken embryonic fibroblast (CEF) cell line cDNA library. The nucleotide sequence of cGPX4 was 802 bp in length with an open reading frame (ORF) that encoded 170 amino acids but lacked the N-terminal domain that encoded the mitochondrial leader sequence (MLS). Chicken non-mitochondrial GPX4 was highly expressed in brain and stromal tissues. Surprisingly, it was found that ovarian stromal tissue cGPX4 expression is regulated quite differently according to the reproductive status of the bird, suggesting that GPX4 may play an important role in reproduction in response to steroid hormones, in addition to its general antioxidant functions.