Gemfibrozil increases the specific binding of rat-cortex nuclear extracts to a PPRE probe.
PPAR agonists have been shown to elicit beneficial responses in several cell- and tissue-models of neurotoxicity. To determine if brain PPARs are responsive to the in vivo administration of PPAR agonists in a similar way to those receptors present in other anatomical localizations, such as liver, we fed rats with gemfibrozil incorporated in the diet at a dose that activates hepatic PPARalpha and produces its typical hypolipidemic effect. Rat cortex nuclear extracts presented a pattern of two specific shifted bands when incubated with a PPRE oligonucleotide. Samples from gemfibrozil-treated rats showed a significant increase in the intensity of the two shifted bands regarding control values (2.4- and 1.8-fold for the specific bands 1 and 2, respectively), indicating that orally administered gemfibrozil reaches brain tissues at concentrations sufficient to increase the specific binding of cortex nuclear extracts to an oligonucleotide mimicking a bona fide PPRE, although no changes in cortex ACO mRNA levels were produced.
D042962:Acyl-CoA Oxidase; D000284:Administration, Oral; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D015248:Gemfibrozil / Q000008:administration & dosage / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010088:Oxidoreductases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D000960:Hypolipidemic Agents; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D010088:Oxidoreductases; D042962:Acyl-CoA Oxidase; D015248:Gemfibrozil