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.