000114905 001__ 114905
000114905 005__ 20190527135626.0
000114905 0247_ $$2doi$$a10.1074/jbc.M502649200
000114905 037__ $$aARTICLE
000114905 245__ $$aPromoter rearrangements cause species-specific hepatic regulation of the glyoxylate reductase/hydroxypyruvate reductase gene by the peroxisome proliferator-activated receptor alpha
000114905 269__ $$a2005
000114905 260__ $$c2005
000114905 336__ $$aJournal Articles
000114905 500__ $$aCenter for Integrative Genomics, University of Lausanne, CH-1015 Lausanne, Switzerland.
000114905 520__ $$aIn liver, the glyoxylate cycle contributes to two metabolic functions, urea and glucose synthesis. One of the key enzymes in this pathway is glyoxylate reductase/hydroxypyruvate reductase (GRHPR) whose dysfunction in human causes primary hyperoxaluria type 2, a disease resulting in oxalate accumulation and formation of kidney stones. In this study, we provide evidence for a transcriptional regulation by the peroxisome proliferator-activated receptor alpha (PPARalpha) of the mouse GRHPR gene in liver. Mice fed with a PPARalpha ligand or in which PPARalpha activity is enhanced by fasting increase their GRHPR gene expression via a peroxisome proliferator response element located in the promoter region of the gene. Consistent with these observations, mice deficient in PPARalpha present higher plasma levels of oxalate in comparison with their wild type counterparts. As expected, the administration of a PPARalpha ligand (Wy-14,643) reduces the plasma oxalate levels. Surprisingly, this effect is also observed in null mice, suggesting a PPARalpha-independent action of the compound. Despite a high degree of similarity between the transcribed region of the human and mouse GRHPR gene, the human promoter has been dramatically reorganized, which has resulted in a loss of PPARalpha regulation. Overall, these data indicate a species-specific regulation by PPARalpha of GRHPR, a key gene of the glyoxylate cycle.
000114905 700__ $$aGenolet, R.
000114905 700__ $$aKersten, S.
000114905 700__ $$aBraissant, O.
000114905 700__ $$aMandard, S.
000114905 700__ $$aTan, N. S.
000114905 700__ $$0244404$$g113607$$aBucher, P.
000114905 700__ $$aDesvergne, B.
000114905 700__ $$aMichalik, L.
000114905 700__ $$aWahli, W.
000114905 773__ $$j280$$tJournal of Biological Chemistry$$k25$$q24143-52
000114905 909C0 $$xU11780$$0252244$$pGR-BUCHER
000114905 909CO $$pSV$$particle$$ooai:infoscience.tind.io:114905
000114905 937__ $$aGR-BUCHER-ARTICLE-2005-002
000114905 973__ $$rREVIEWED$$sPUBLISHED$$aOTHER
000114905 980__ $$aARTICLE