Peroxisome proliferator-activated receptor alpha-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 (PPARalpha) 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 PPARalpha (PPARalpha-/-), suggesting a regulatory role for PPARalpha 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.
Dadras
S S
SS
Department of Pathology, Northwestern University Medical School, Chicago, IL 60611-3008, USA.
Cook
W S
WS
Yeldandi
A V
AV
Cao
W Q
WQ
Rao
M S
MS
Wang
Z
Z
Reddy
J K
JK
D042962:Acyl-CoA Oxidase; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D017353:Gene Deletion; D017403:In Situ Hybridization; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D020025:Peroxisome Proliferators / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D000950:Antigens, Ly; D020025:Peroxisome Proliferators; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D010088:Oxidoreductases; D042962:Acyl-CoA Oxidase