Promoter rearrangements cause species-specific hepatic regulation of the glyoxylate reductase/hydroxypyruvate reductase gene by the peroxisome proliferator-activated receptor alpha.

Détails

ID Serval
serval:BIB_038A574254CF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Promoter rearrangements cause species-specific hepatic regulation of the glyoxylate reductase/hydroxypyruvate reductase gene by the peroxisome proliferator-activated receptor alpha.
Périodique
Journal of Biological Chemistry
Auteur(s)
Genolet R., Kersten S., Braissant O., Mandard S., Tan N.S., Bucher P., Desvergne B., Michalik L., Wahli W.
ISSN
0021-9258
Statut éditorial
Publié
Date de publication
2005
Peer-reviewed
Oui
Volume
280
Numéro
25
Pages
24143-24152
Langue
anglais
Notes
Publication types: Journal Article
Résumé
In liver, the glyoxylate cycle contributes to two metabolic functions, urea and glucose synthesis. One of the key enzymes in this pathway is glyoxylate reductase/hydroxypyruvate reductase (GRHPR) whose dysfunction in human causes primary hyperoxaluria type 2, a disease resulting in oxalate accumulation and formation of kidney stones. In this study, we provide evidence for a transcriptional regulation by the peroxisome proliferator-activated receptor alpha (PPARalpha) of the mouse GRHPR gene in liver. Mice fed with a PPARalpha ligand or in which PPARalpha activity is enhanced by fasting increase their GRHPR gene expression via a peroxisome proliferator response element located in the promoter region of the gene. Consistent with these observations, mice deficient in PPARalpha present higher plasma levels of oxalate in comparison with their wild type counterparts. As expected, the administration of a PPARalpha ligand (Wy-14,643) reduces the plasma oxalate levels. Surprisingly, this effect is also observed in null mice, suggesting a PPARalpha-independent action of the compound. Despite a high degree of similarity between the transcribed region of the human and mouse GRHPR gene, the human promoter has been dramatically reorganized, which has resulted in a loss of PPARalpha regulation. Overall, these data indicate a species-specific regulation by PPARalpha of GRHPR, a key gene of the glyoxylate cycle.
Mots-clé
Alcohol Oxidoreductases/genetics, Animals, Base Sequence, Cloning, Molecular, DNA, DNA Primers, Gene Expression Regulation, Enzymologic/genetics, Humans, Hydroxypyruvate Reductase, Liver/enzymology, Mice, Mice, Knockout, Molecular Sequence Data, PPAR alpha/physiology, Promoter Regions, Genetic, Sequence Homology, Nucleic Acid, Species Specificity
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 15:26
Dernière modification de la notice
20/08/2019 12:25
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