The transcription of the peroxisome proliferator- activated receptor a gene is regulated by protein kinase C

The transcriptional regulation of peroxisome proliferator-activated recepto r alpha (PPAR alpha) by a variety of peroxisome proliferators was investiga ted. The treatment of primary cultures of rat hepatocytes with Wyl4,643 or clofibrate increased mRNA steady state levels of both PPAR alpha and acyl c oenzyme A oxidase (ACOX). In contrast, fenofibrate and ciprofibrate increas ed the expression of A COX without affecting that of PPAR alpha. Inhibition of protein kinase C (PKC) activity using bisindolylmaleimide or calphostin C abolished the increased PPAR alpha expression by the peroxisome prolifer ators whereas the expression of the ACOX gene remained unaffected. Phorbol- 12-myristate-13-acetate increased PPAR alpha mRNA levels without altering A COX mRNA levels. It can thus be concluded that a number of peroxisome proli ferators activate a PKC-dependent signalling pathway in addition to the PPA R alpha pathway. The PKC signal transduction pathway contributes to the reg ulation of PPAR alpha expression but does not influence the transcriptional activity of PPAR alpha. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.