Peroxisome proliferator-activated receptor (PPAR)-dependent and -independent transcriptional modulation of several non-peroxisomal genes by peroxisome proliferators.
To better characterize peroxisome proliferator-induced non-peroxisomal responses, we searched the mRNAs of which the levels were modulated by proliferators. We used the PCR-based methods including differential display. The mRNAs were divided into at least four groups by their time-courses of induction and repression: group 1 very rapidly increased then decreased; group 2 increased after a time lag (well-characterized peroxisomal mRNAs belonged to this group); group 3 decreased reciprocally compared with group 2 mRNAs; group 4 increased after group 2 mRNAs, with a much longer lag period. All of these modulations cannot be explained by peroxisome proliferator action through PPAR and RXR dimerization on the target genes to activate transcription. Another unidentified transcription factor may be involved in some of these modulations. It will also be important to consider PPAR-independent pathways when studying the diverse effects of peroxisome proliferators.
Motojima
K
K
Department of Biochemistry, School of Pharmaceutical Sciences, Toho University, Chiba, Japan.
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D003001:Cloning, Molecular; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D013997:Time Factors; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
D000924:Anticholesteremic Agents; D011743:Pyrimidines; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C006253:pirinixic acid