Search results for "PEROXISOME"

Telmisartan as metabolic modulator: a new perspective in sports doping?

2011

The World Antidoping Agency (WADA) has introduced some changes in the 2012 prohibited list. Among the leading innovations to the rules are that both 5-aminoimidazole-4-carboxamide-1-[beta]-D-ribofuranoside (peroxisome proliferator�activated receptor-[delta] [PPAR-[delta]]-5' adenosine monophosphate-activated protein kinase [AMPK] agonist) and GW1516 (PPAR-[delta]-agonist) are no longer categorized as gene doping substances in the new 2012 prohibited list but as metabolic modulators in the class �Hormone and metabolic modulators.� This may also be valid for the angotensin II receptor blocker telmisartan. It has recently been shown that telmisartan might induce similar biochemical, biological…

LXR antagonists induce ABCD2 expression

2014

X-linked adrenoleukodystrophy (X-ALD) is a rare neurodegenerative disorder characterized by the accumulation of very-long-chain fatty acids resulting from a beta-oxidation defect. Oxidative stress and inflammation are also key components of the pathogenesis. X-ALD is caused by mutations in the ABCDI gene, which encodes for a peroxisomal half ABC transporter predicted to participate in the entry of VLCFA-CoA into the peroxisome, the unique site of their beta-oxidation. Two homologous peroxisomal ABC transporters, ABCD2 and ABCD3 have been proven to compensate for ABCD1 deficiency when overexpressed. Pharmacological induction of these target genes could therefore represent an alternative ther…

Glycogen synthase 2 is a novel target gene of peroxisome proliferator-activated receptors.

2007

International audience; Glycogen synthase 2 (Gys-2) is the ratelimiting enzyme in the storage of glycogen in liver and adipose tissue, yet little is known about regulation of Gys-2 transcription. The peroxisome proliferator-activated receptors (PPARs) are transcription factors involved in the regulation of lipid and glucose metabolism and might be hypothesized to govern glycogen synthesis as well. Here, we show that Gys-2 is a direct target gene of PPARalpha, PPARbeta/delta and PPARgamma. Expression of Gys-2 is significantly reduced in adipose tissue of PPARalpha-/-, PPARbeta/delta-/- and PPARgamma+/- mice. Furthermore, synthetic PPARbeta/delta, and gamma agonists markedly up-regulate Gys-2…

Polycerasoidol, a Natural Prenylated Benzopyran with a Dual PPARα/PPARγ Agonist Activity and Anti-inflammatory Effect

2019

Dual peroxisome proliferator-activated receptor-α/γ (PPARα/γ) agonists regulate both lipid and glucose homeostasis under different metabolic conditions and can exert anti-inflammatory activity. We investigated the potential dual PPARα/γ agonism of prenylated benzopyrans polycerasoidol (1) and polycerasoidin (2) and their derivatives for novel drug development. Nine semisynthetic derivatives were prepared from the natural polycerasoidol (1) and polycerasoidin (2), which were evaluated for PPARα, -γ, -δ and retinoid X receptor-α activity in transactivation assays. Polycerasoidol (1) exhibited potent dual PPARα/γ agonism and low cytotoxicity. Structure–activity relationship studies revealed th…

The Peroxisomal 3-keto-acyl-CoA thiolase B Gene Expression Is under the Dual Control of PPARα and HNF4α in the Liver

2011

PPARα and HNF4α are nuclear receptors that control gene transcription by direct binding to specific nucleotide sequences. Using transgenic mice deficient for either PPARα or HNF4α, we show that the expression of the peroxisomal3-keto-acyl-CoA thiolase B(Thb) is under the dependence of these two transcription factors. Transactivation and gel shift experiments identified a novel PPAR response element within intron 3 of theThbgene, by which PPARα but not HNF4α transactivates. Intriguingly, we found that HNF4α enhanced PPARα/RXRα transactivation from TB PPRE3 in a DNA-binding independent manner. Coimmunoprecipitation assays supported the hypothesis that HNF4α was physically interacting with RXR…

Effects of tributyltin(IV) chloride on the gametes and fertilization ofAscidia malaca (Ascidiacea: Tunicata)

2003

Ascidia malaca gametes before fertilization incubated in 10-5 or 10-7 M solutions of tributyltin(IV) chloride, TBTCl, for 3 h appear highly damaged under transmission electron microscopy observation. Also, the fertilization process is affected by the compound: the damaged spermatozoa are present in the vitelline coat and the egg does not cleave. An increase of microbodies, structurally similar to peroxisomes, have been detected in the egg peripheral cytoplasm, probably in relation to their role in alleviating damage to some cellular components. The results have shown that the reproduction of ascidians under unfavourable environmental conditions is prevented. Copyright © 2003 John Wiley &amp…

Peroxisome proliferation in rodents and human: A model of cell organelle biogenesis

1995

Intestinal Fat Absorption: Roles of Intracellular Lipid-Binding Proteins and Peroxisome Proliferator-Activated Receptors

2004

Involvment of docosanoïc acid (C22=0), and of very long chain fatty acids (tetracosanoïc acid (C24=0), hexacosanoïc acid (C26=0) in Alzheimer's disea…

2013

In the brain and in the plasma of patients with Alzheimer’s disease (AD), marked accumulation of C22:0 and of very long chain fatty acids (C24:0 ; C26:0) have been reported. Important decreases of docosahexaenoic acid (DHA; C22:6 n-3) have also been described as well as quantitative and qualitative modifications of plasmalogens. Altogether, these lipid modifications suggest an implication of peroxisomal metabolism disorders in the physiopathology of AD. Therefore, the biological activities of C22:0, C24:0 and C26:0 have been studied on human neuronal cells SK-N-BE. On these cells, the lipotoxicity of fatty acids (C22:0, C24:0 and C26:0) leads to various cellular modifications: topographical…

Chronic peroxisome proliferator-activated receptorβ/δ agonist GW0742 prevents hypertension, vascular inflammatory and oxidative status, and endotheli…

2015

Endothelial dysfunction plays a key role in obesity-induced risk of cardiovascular disease. The aim of the present study was to analyze the effect of chronic peroxisome proliferator-activated receptor (PPAR)β/δ agonist GW0742 treatment on endothelial function in obese mice fed a high-fat diet (HFD).Five-week-old male mice were allocated to one of the following groups: control, control-treated (GW0742, 3 mg/kg per day, by oral gavage), HFD, HFD + GW0742, HFD + GSK0660 (1 mg/kg/day, intraperitoneal) or HFD-GW0742-GSK0660 and followed for 11 or 13 weeks. GW0742 administration to mice fed HFD prevented the gain of body weight, heart and kidney hypertrophy, and fat accumulation. The increase in …