Search results for "peroxisome"

Selenoproteins, cholesterol-lowering drugs, and the consequences: revisiting of the mevalonate pathway.

2004

3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and peroxisome proliferator-activated receptor alpha activators (fibrates) are the backbone of pharmacologic hypercholesterolemia and dyslipidemia treatment. Many of their clinical effects, however, are still enigmatic. This article describes how a side road of the mevalonate pathway, characterized in recent years, can rationalize a major fraction of these unexplained observations. This side road is the enzymatic isopentenylation of selenocysteine-tRNA([Ser]Sec) (Sec-tRNA), the singular tRNA to decode the unusual amino acid selenocysteine. The functionally indispensable isopentenylation of Sec-tRNA requires a unique interm…

Dehydroepiandrosterone Induction of the Abcd2 and Abcd3 Genes encoding peroxisomal ABC Transporters

2003

Dehydroepiandrosterone (DHEA) is a peroxisome proliferator known to increase the expression of the genes encoding the peroxisomal s-oxidation enzymes in rodents. Using RT-PCR, we analysed the expression of the Abcd2 and Abcd3 genes encoding the peroxisomal ABC transporters ALDRP (ALD related protein) and PMP70 (70 kDa peroxisomal membrane protein) in primary cultures of rats hepatocytes treated with sulfated DHEA. We observed a time (12-72h) and dose (125-500μM) dependent increase in the expression of both genes.

2004

β-oxidation of long and very long chain fatty acyl-CoA derivatives occurs in peroxisomes, which are ubiquitous subcellular organelles of eukaryotic cells. This pathway releases acetyl-CoA as precursor for several key molecules such as cholesterol. Numerous enzymes participating to cholesterol and fatty acids biosynthesis pathways are co-localized in peroxisomes and some of their encoding genes are known as targets of the NFY transcriptional regulator. However, until now no interaction between NFY transcription factor and genes encoding peroxisomal β-oxidation has been reported. This work studied the interactions between NFY factor with the rat gene promoters of two enzymes of the fatty acid…

Genetic-dependency of peroxisomal cell functions - emerging aspects

2003

This paper reviews aspects concerning the genetic regulation of the expression of the well studied peroxisomal genes including those of fatty acid beta-oxidation enzymes; acyl-CoA oxidase, multifunctional enzyme and thiolase from different tissues and species. An important statement is PPARalpha, which is now long known to be in rodents the key nuclear receptor orchestrating liver peroxisome proliferation and enhanced peroxisomal beta-oxidation, does not appear to control so strongly in man the expression of genes involved in peroxisomal fatty acid beta-oxidation related enzymes. In this respect, the present review strengthens among others the emerging concept that, in the humans, the main …

Regulation of Farnesyl Diphosphate Synthase Gene Expression by Fatty Acids

2003

Cholesterol biosynthesis depends on the activity of regulatory enzymes, including the peroxisomal Farnesyl Diphosphate Synthase (FPPS ). Cholesterol regulates its own synthesis rate. Hence, as a response to cholesterol depletion, a feed back mechanism is activated, whereby sterol regulatory binding proteins (SREBPla, 1c and 2 ) are subjected to sequential proteolytic activation, which permits their interaction with specific DNA response elements from responsive genes. In turn, the transcriptional activity of cholesterol biosynthesis genes is induced. Conversely, cholesterol accumulation decreases SREBP maturation and transcription of controlled genes. In addition, polyunsaturated fatty acid…

Mammalian Xenobiotic Epoxide Hydrolases

2002

PPARgamma agonist pioglitazone does not enhance performance in mice

2013

Peroxisome-proliferator-activated receptor (PPAR) delta and adenosine monophosphate (AMP)-activated protein kinases (AMPKs) regulate the metabolic and contractile characteristics of myofibres. PPAR proteins are nuclear receptors that function as transcription factors and regulate the expression of multiple genes. AMPK has been described as a master metabolic regulator which also controls gene expression through the direct phosphorylation of some nuclear proteins. Since it was discovered that both PPARdelta agonists (GW1516) and AMPK activators (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, known as AICAR) are very effective performance-enhancing substances in sedentary mice, the Worl…

PPARs as physiological sensors of fatty acid metabolism molecular regulation in peroxisomes

2001

Substrate specificity overlap and interaction between Adrenoleukodystrophy protein (ALDP/ABCD1) and Adrenoleukodystrophy-related protein (ALDRP/ABCD2)

2011

X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder caused by mutations in the ABCD1 gene, which encodes a peroxisomal member of the ATP-binding cassette (ABC) transporter subfamily D called ALDP. ALDP is supposed to function as a homodimer allowing the entry of CoA-esters of very-long chain fatty acids (VLCFA) into the peroxisome, the unique site of their β-oxidation. ALDP deficiency can be corrected by overexpression of ALDRP, its closest homolog. However, the exact nature of the substrates transported by ALDRP and its relationships with ALDP still remain unclear. To gain insight into the function of ALDRP, we used cell models allowing the induction in a dose-dependent m…

Evidence of oxidative stress in very long chain fatty acid--treated oligodendrocytes and potentialization of ROS production using RNA interference-di…

2011

X-linked adrenoleukodystrophy (X-ALD) and pseudo neonatal adrenoleukodystrophy (P-NALD) are neurodegenerative demyelinating diseases resulting from the functional loss of the peroxisomal ATP-binding cassette transporter D (ABCD1) and from single peroxisomal enzyme deficiency (Acyl-CoA oxidase1: ACOX1), respectively. As these proteins are involved in the catabolism of very long chain fatty acids (VLCFA: C24:0, C26:0), X-ALD and P-NALD patients are characterized by the accumulation of VLCFA in plasma and tissues. Since peroxisomes are involved in the metabolism of reactive oxygen species (ROS) and nitrogen species (RNS), we examined the impact of VLCFA on the oxidative status of 158N murine o…