Analytical subcellular fractionation of microglial BV-2 cells with peroxisomal beta-oxidation defect.

Peroxisomes have gained increasing attention and are now considered vital players in normal physiological functions. To gain further insight into how peroxisomal defects influence cellular functions, we developed BV-2 microglial models featuring CRISPR/Cas9 gene-edited mutations in peroxisomal Acox1 or Abcd1 and Abcd2 genes. The Acox1 BV-2 cell line we generated lacks acyl-CoA oxidase 1, the key enzyme that initiates peroxisomal β-oxidation.

Molecular and Cellular Characterization of the Glutathione Transferases Involved in the Olfactory Metabolism of the Mammary Pheromone.

Odorant metabolizing enzymes, considered as critical olfactory perireceptor actors, control the odor molecules reaching the olfactory epithelium by biotransforming them. As an odorant, the mammary pheromone, i.e.

Glutathione Transferase Omega 1 Localization in Oral Tissues and Interactions with Food Phytochemicals.

Glutathione transferases are xenobiotic-metabolizing enzymes with both glutathione-conjugation and ligandin roles. GSTs are present in chemosensory tissues and fluids of the nasal/oral cavities where they protect tissues from exogenous compounds, including food molecules. In the present study, we explored the presence of the omega-class glutathione transferase (GSTO1) in the rat oral cavity.

Correction: The odorant metabolizing enzyme UGT2A1: Immunolocalization and impact of the modulation of its activity on the olfactory response.

[This corrects the article DOI: 10.1371/journal.pone.

In Vitro Evaluation of the Effects of 7-Ketocholesterol and 7β-Hydroxycholesterol on the Peroxisomal Status: Prevention of Peroxisomal Damages and Concept of Pexotherapy.

7-Ketocholesterol and 7β-hydroxycholesterol are most often derived from the autoxidation of cholesterol. Their quantities are often increased in the body fluids and/or diseased organs of patients with age-related diseases such as cardiovascular diseases, Alzheimer's disease, age-related macular degeneration, and sarcopenia which are frequently associated with a rupture of RedOx homeostasis leading to a high oxidative stress contributing to cell and tissue damages. On murine cells from the central nervous system (158N oligodendrocytes, microglial BV-2 cells, and neuronal N2a cells) as well as on C2C12 murine myoblasts, these two oxysterols can induce a mode of cell death which is associated with qualitative, quantitative, and functional modifications of the peroxisome.

Nasal Odorant Competitive Metabolism Is Involved in the Human Olfactory Process.

Within the peripheral olfactory process, odorant metabolizing enzymes are involved in the active biotransformation of odorants, thus influencing the intensity and quality of the signal, but little evidence exists in humans. Here, we characterized the fast nasal metabolism of the food aroma pentane-2,3-dione and identified two resulting metabolites in the nasal-exhaled air, supporting the metabolizing role of the dicarbonyl/l-xylulose reductase. We showed , using the recombinant enzyme, that pentane-2,3-dione metabolism was inhibited by a second odorant (e.

Antioxidant Properties and Cytoprotective Effect of L. Seed Oil against 7β-Hydroxycholesterol-Induced Toxicity in C2C12 Myoblasts: Reduction in Oxidative Stress, Mitochondrial and Peroxisomal Dysfunctions and Attenuation of Cell Death.

Aging is characterized by a progressive increase in oxidative stress, which favors lipid peroxidation and the formation of cholesterol oxide derivatives, including 7β-hydroxycholesterol (7β-OHC). This oxysterol, which is known to trigger oxidative stress, inflammation, and cell death, could contribute to the aging process and age-related diseases, such as sarcopenia. Identifying molecules or mixtures of molecules preventing the toxicity of 7β-OHC is therefore an important issue.

The odorant metabolizing enzyme UGT2A1: Immunolocalization and impact of the modulation of its activity on the olfactory response.

Odorant metabolizing enzymes (OMEs) are expressed in the olfactory epithelium (OE) where they play a significant role in the peripheral olfactory process by catalyzing the fast biotransformation of odorants leading either to their elimination or to the synthesis of new odorant stimuli. The large family of OMEs gathers different classes which interact with a myriad of odorants alike and complementary to olfactory receptors. Thus, it is necessary to increase our knowledge on OMEs to better understand their function in the physiological process of olfaction.

7-Ketocholesterol- and 7β-Hydroxycholesterol-Induced Peroxisomal Disorders in Glial, Microglial and Neuronal Cells: Potential Role in Neurodegeneration : 7-ketocholesterol and 7β-hydroxycholesterol-Induced Peroxisomal Disorders and Neurodegeneration.

Peroxisomopathies are qualitative or quantitative deficiencies in peroxisomes which lead to increases in the level of very-long-chain fatty acids (VLCFA) and can be associated with more or less pronounced dysfunction of central nervous system cells: glial and microglial cells. Currently, in frequent neurodegenerative diseases, Alzheimer's disease (AD) and multiple sclerosis (MS), peroxisomal dysfunction is also suspected due to an increase in VLCFA, which can be associated with a decrease of plasmalogens, in these patients. Moreover, in patients suffering from peroxisomopathies, such as X-linked adrenoleukodystrophy (X-ALD), AD, or MS, the increase in oxidative stress observed leads to the formation of cytotoxic oxysterols: 7-ketocholesterol (7KC) and 7β-hydroxycholesterol (7β-OHC).

Interactions Between Odorants and Glutathione Transferases in the Human Olfactory Cleft.

Xenobiotic metabolizing enzymes and other proteins, including odorant-binding proteins located in the nasal epithelium and mucus, participate in a series of processes modulating the concentration of odorants in the environment of olfactory receptors (ORs) and finely impact odor perception. These enzymes and transporters are thought to participate in odorant degradation or transport. Odorant biotransformation results in 1) changes in the odorant quantity up to their clearance and the termination of signaling and 2) the formation of new odorant stimuli (metabolites).

Protein expression in submandibular glands of young rats is modified by a high-fat/high-sugar maternal diet.

Objective: Maternal diet has consequences on many organs of the offspring, but salivary glands have received little attention despite the importance of the saliva secretory function in oral health and control of food intake. The objective of this work was therefore to document in rats the impact of maternal high-fat/high-sugar diet (Western Diet) on submandibular glands of the progeny.

Design: Sprague-Dawley rat dams were fed either a Western diet or control diet during gestation and lactation and their pups were sacrificed 25 days after birth.

Induction of peroxisomal changes in oligodendrocytes treated with 7-ketocholesterol: Attenuation by α-tocopherol.

The involvement of organelles in cell death is well established especially for endoplasmic reticulum, lysosomes and mitochondria. However, the role of the peroxisome is not well known, though peroxisomal dysfunction favors a rupture of redox equilibrium. To study the role of peroxisomes in cell death, 158 N murine oligodendrocytes were treated with 7-ketocholesterol (7 KC: 25-50 μM, 24 h).

Recombinant human plasma phospholipid transfer protein (PLTP) to prevent bacterial growth and to treat sepsis.

Although plasma phospholipid transfer protein (PLTP) has been mainly studied in the context of atherosclerosis, it shares homology with proteins involved in innate immunity. Here, we produced active recombinant human PLTP (rhPLTP) in the milk of new lines of transgenic rabbits. We successfully used rhPLTP as an exogenous therapeutic protein to treat endotoxemia and sepsis.

Oral homeostasis disruption by medical plasticizer component bisphenol A in adult male rats.

Objectives/hypothesis: Bisphenol A (BPA) is a synthetic estrogen-like chemical mimetic widely used in the manufacture of polycarbonate plastics and epoxy resins found in numerous consumer products including food packaging, medical devices, and dental sealants. Because it is recovered in fluids and it can reach high levels in saliva, this study aimed to evaluate its safety on oral homeostasis by examining its effects on salivary glands, mouth epithelium, water consumption, and salt preference, each parameter being estrogen sensitive.

Study Design: Randomized controlled trial involving rats.

Odorant metabolism catalyzed by olfactory mucosal enzymes influences peripheral olfactory responses in rats.

A large set of xenobiotic-metabolizing enzymes (XMEs), such as the cytochrome P450 monooxygenases (CYPs), esterases and transferases, are highly expressed in mammalian olfactory mucosa (OM). These enzymes are known to catalyze the biotransformation of exogenous compounds to facilitate elimination. However, the functions of these enzymes in the olfactory epithelium are not clearly understood.

Incidence of Abcd1 level on the induction of cell death and organelle dysfunctions triggered by very long chain fatty acids and TNF-α on oligodendrocytes and astrocytes.

X-linked adrenoleukodystrophy (X-ALD) is characterized by ABCD1 deficiency. This disease is associated with elevated concentrations of very long chain fatty acids (C24:0 and C26:0) in the plasma and tissues of patients. Under its severe form, brain demyelination and inflammation are observed.

Expression and differential localization of xenobiotic transporters in the rat olfactory neuro-epithelium.

Transporters, such as multidrug resistance P-glycoproteins (MDR), multidrug resistance-related proteins (MRP) and organic anion transporters (OATs), are involved in xenobiotic metabolism, particularly the cellular uptake or efflux of xenobiotics (and endobiotics) or their metabolites. The olfactory epithelium is exposed to both inhaled xenobiotics and those coming from systemic circulation. This tissue has been described as a pathway for xenobiotics to the brain via olfactory perineural space.

Impact of 7-ketocholesterol and very long chain fatty acids on oligodendrocyte lipid membrane organization: evaluation via LAURDAN and FAMIS spectral image analysis.

In the context of multiple sclerosis and X-linked adrenoleukodystrophy, 7-ketocholesterol (7KC) and very long chain fatty acids (C24:0, C26:0) are supposed to induce side effects respectively on oligodendrocytes which are myelin (which is a lipoproteic complex) synthesizing cells. The effects of 7KC (25, 50 μM), C24:0 and C26:0 (10, 20 μM) on cell viability and lipid membrane organization were investigated on 158N murine oligodendrocytes. Concerning 7KC and fatty acids (at 20 μM only): 1) cell growth was strongly inhibited; 2) marked induction of cell death was revealed with propidium iodide (PI); 3) no apoptotic cells were found with C24:0 and C26:0 (absence of cells with condensed and/or fragmented nuclei, of FLICA positive cells and of PI negative/SYTO16 negative cells); 4) some apoptotic cells were detected with 7KC.

Effect of a chronic cholesterol-rich diet on vascular structure and oxidative stress in LDLR-/- mice.

Aims: There is conflicting evidence regarding the relationship between hypercholesterolemia and oxidative stress in vessels. To test the potential relationship, a mouse model of hypercholesterolemia was used.

Methods: Low density lipoprotein receptor-deficient (LDLR(-/-)) and control (C57Bl/6) mice were fed a normal or (1.

Worsening of diet-induced atherosclerosis in a new model of transgenic rabbit expressing the human plasma phospholipid transfer protein.

Objective: Plasma phospholipid transfer protein (PLTP) is involved in intravascular lipoprotein metabolism. PLTP is known to act through 2 main mechanisms: by remodeling high-density lipoproteins (HDL) and by increasing apolipoprotein (apo) B-containing lipoproteins. The aim of this study was to generate a new model of human PLTP transgenic (HuPLTPTg) rabbit and to determine whether PLTP expression modulates atherosclerosis in this species that, unlike humans and mice, displays naturally very low PLTP activity.

Human luteinized granulosa cells secrete apoB100-containing lipoproteins.

Thus far, liver, intestine, heart, and placenta have been shown to secrete apolipoprotein (apo)B-containing lipoproteins. In the present study, we first investigated lipoproteins in human follicular fluid (FF), surrounding developing oocytes within the ovary, as well as in corresponding plasma samples (n = 12). HDL cholesterol within FF correlated well with plasma HDL cholesterol (r = 0.

Peroxisomal and mitochondrial status of two murine oligodendrocytic cell lines (158N, 158JP): potential models for the study of peroxisomal disorders associated with dysmyelination processes.

In some neurodegenerative disorders (leukodystrophies) characterized by myelin alterations, the defect of peroxisomal functions on myelin-producing cells (oligodendrocytes) are poorly understood. The development of in vitro models is fundamental to understanding the physiopathogenesis of these diseases. We characterized two immortalized murine oligodendrocyte cell lines: a normal (158N) and a jimpy (158JP) cell line mutated for the proteolipid protein PLP/DM20.