Peroxisome proliferator-activated receptor α-dependent induction of cell surface antigen Ly-6D gene in the mouse liver

Spontaneous peroxisome proliferation-related pleiotropic responses occurring in the liver of mice lacking peroxisomal fatty acyl-CoA oxidase (AOX(-/-)) are attributed to sustained activation of peroxisome proliferator-activated receptor alpha (PPAR alpha) by its putative natural ligands that require AOX for their metabolism In this study, using a gene expression screen, we show that Ly-6 (lymphocyte antigen 6 complex, locus D; mouse ThB), which belongs to a distinctive family of low molecular weight phosphatidyl inositol anchored cell surface glycoproteins, is upregulated in mouse liver with peroxisome proliferation. Increases in Ly-6D mRNA levels are observed in AOX(-/-) mouse liver with spontaneous peroxisome proliferation and also in the liver of wild-type mice treated with synthetic: peroxisome proliferators. Peroxisome proliferators failed to increase hepatic Ly-6D mRNA levels in mice lacking PPARa (PPAR alpha (-/-)), suggesting a regulatory role for PPAR alpha in the induction of Ly-6D. These observations suggest that changes in certain cell surface proteins also form part of the pleiotropic responses associated with peroxisome proliferation.