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...

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Veröffentlicht in:Life sciences (1973) 2003-10, Vol.73 (23), p.2927-2937
Hauptverfasser: Sanguino, Elena, Ramón, Miguel, Roglans, Núria, Alegret, Marta, Sánchez, Rosa M, Vázquez-Carrera, Manuel, Laguna, Juan C
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container_end_page 2937
container_issue 23
container_start_page 2927
container_title Life sciences (1973)
container_volume 73
creator Sanguino, Elena
Ramón, Miguel
Roglans, Núria
Alegret, Marta
Sánchez, Rosa M
Vázquez-Carrera, Manuel
Laguna, Juan C
description 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 PPARα 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.
doi_str_mv 10.1016/j.lfs.2003.04.001
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subjects ACO
Acyl-CoA Oxidase
Administration, Oral
Animals
Cell Nucleus - drug effects
Cell Nucleus - metabolism
Cerebral Cortex - drug effects
Cerebral Cortex - metabolism
Fibrates
Gemfibrozil
Gemfibrozil - administration & dosage
Gemfibrozil - pharmacology
Hypolipidemic Agents - administration & dosage
Hypolipidemic Agents - pharmacology
Male
Oxidoreductases - metabolism
PPAR
Rat cortex
Rats
Rats, Sprague-Dawley
Receptors, Cytoplasmic and Nuclear - genetics
Receptors, Cytoplasmic and Nuclear - metabolism
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - metabolism
Transcription Factors - genetics
Transcription Factors - metabolism
title Gemfibrozil increases the specific binding of rat-cortex nuclear extracts to a PPRE probe
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