The transcription of the peroxisome proliferator-activated receptor alpha gene is regulated by protein kinase C.
The transcriptional regulation of peroxisome proliferator-activated receptor alpha (PPARalpha) by a variety of peroxisome proliferators was investigated. The treatment of primary cultures of rat hepatocytes with Wy14,643 or clofibrate increased mRNA steady state levels of both PPARalpha and acyl coenzyme A oxidase (ACOX). In contrast, fenofibrate and ciprofibrate increased the expression of ACOX without affecting that of PPARalpha. Inhibition of protein kinase C (PKC) activity using bisindolylmaleimide or calphostin C abolished the increased PPARalpha expression by the peroxisome proliferators whereas the expression of the ACOX gene remained unaffected. Phorbol-12-myristate-13-acetate increased PPARalpha mRNA levels without altering ACOX mRNA levels. It can thus be concluded that a number of peroxisome proliferators activate a PKC-dependent signalling pathway in addition to the PPARalpha pathway. The PKC signal transduction pathway contributes to the regulation of PPARalpha expression but does not influence the transcriptional activity of PPARalpha.
Yaacob
N S
NS
School of Biomedical and Life Sciences, University of Surrey, Surrey GU2 7XH, Guildford, UK.
Norazmi
M N
MN
Gibson
G G
GG
Kass
G E
GE
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D020025:Peroxisome Proliferators / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
D020025:Peroxisome Proliferators; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium