0000000000144488
AUTHOR
Ginette Bessède
Evidence of oxidative stress in very long chain fatty acid--treated oligodendrocytes and potentialization of ROS production using RNA interference-directed knockdown of ABCD1 and ACOX1 peroxisomal proteins.
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…
Mass Concentration of Plasma Phospholipid Transfer Protein in Normolipidemic, Type IIa Hyperlipidemic, Type IIb Hyperlipidemic, and Non–Insulin-Dependent Diabetic Subjects as Measured by a Specific ELISA
Abstract —Mean plasma phospholipid transfer protein (PLTP) concentrations were measured for the first time by using a competitive enzyme-linked immunosorbent assay. PLTP mass levels and phospholipid transfer activity values, which were significantly correlated among normolipidemic plasma samples ( r =0.787, P <0.0001), did not differ between normolipidemic subjects (3.95±1.04 mg/L and 575±81 nmol · mL −1 · h −1 , respectively; n=30), type IIa hyperlipidemic patients (4.06±0.84 mg/L and 571±43 nmol · mL −1 · h −1 , respectively; n=36), and type IIb hyperlipidemic patients (3.90±0.79 mg/L and 575±48 nmol · mL −1 · h −1 , respectively; n=33). No significant correlations with plasma lipid p…
Knock-down of the oxysterol receptor LXRα impairs cholesterol efflux in human primary macrophages: lack of compensation by LXRβ activation.
Liver X Receptors (LXRs) α and β are oxysterol-activated nuclear receptors involved in the control of lipid metabolism and inflammation. Pharmacological activation of LXR is promising in the treatment of atherosclerosis since it can promote cholesterol efflux from macrophages and prevent foam cell formation. However, the development of LXR agonists has been limited by undesirable side-effects such as hepatic steatosis mediated by LXRα activation. Therefore, it has been proposed that targeting LXRα activators to extrahepatic tissues or using LXRβ-specific activators could be used as alternative strategies. It is not clear whether these molecules will retain the full atheroprotective potentia…
Induction of Transglutaminase 2 by a Liver X Receptor/Retinoic Acid Receptor α Pathway Increases the Clearance of Apoptotic Cells by Human Macrophages
Rationale: Liver X receptors (LXRs) are oxysterol-activated nuclear receptors that are involved in the control of cholesterol homeostasis and inflammatory response. Human monocytes and macrophages express high levels of these receptors and are appropriate cells to study the response to LXR agonists. Objective: The purpose of this study was to identify new LXR targets in human primary monocytes and macrophages and the consequences of their activation. Methods and Results: We show that LXR agonists significantly increase the mRNA and protein levels of the retinoic acid receptor (RAR)α in primary monocytes and macrophages. LXR agonists promote RARα gene transcription through binding to a spec…
Cholesterol accumulation is increased in macrophages of phospholipid transfer protein-deficient mice: normalization by dietary alpha-tocopherol supplementation.
Objective— Phospholipid transfer protein (PLTP) is a multifunctional, extracellular lipid transport protein that plays a major role in lipoprotein metabolism and atherosclerosis. Recent in vivo studies suggested that unlike systemic PLTP, macrophage-derived PLTP would be antiatherogenic. The present study aimed at characterizing the atheroprotective properties of macrophage-derived PLTP. Methods and Results— Peritoneal macrophages were isolated from PLTP-deficient and wild-type mice and their biochemical characteristics were compared. It is shown that macrophages isolated from PLTP-deficient mice have increased basal cholesterol content and accumulate more cholesterol in the presence of LD…