Singlet Molecular Oxygen Reactions with Nucleic Acids, Lipids, and Proteins

Chemical Reviews, Journal Year: 2019, Volume and Issue: 119(3), P. 2043 - 2086

Published: Feb. 5, 2019

Singlet oxygen (1O2) is a biologically relevant reactive species capable of efficiently reacting with cellular constituents. The resulting oxidatively generated damage to nucleic acids, membrane unsaturated lipids, and protein components has been shown be implicated in several diseases, including arthritis, cataracts, skin cancer. may endogenously produced, among various possibilities, by myeloperoxidase, an enzyme inflammation processes, also the UVA component solar radiation through photosensitization reactions. Emphasis placed this Review on description main oxidation reactions initiated 1O2 modifications within key targets, guanine for targeted amino acids. Most these give rise peroxides dioxetanes, whose formation rationalized terms [4+2] cycloaddition 1,2-cycloaddition dienes + olefins, respectively. use [18O]-labeled thermolabile endoperoxides as source applied study mechanistic aspects preferential targets biological systems. A major topic deals search molecular signature biomolecules cells. It anticipated that labeled association sensitive mass spectrometric methods should constitute powerful tools purpose.

Language: Английский

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Human Milk Lipids

Annals of Nutrition and Metabolism, Journal Year: 2016, Volume and Issue: 69(Suppl. 2), P. 27 - 40

Published: Jan. 1, 2016

Human milk lipids provide the infant with energy and essential vitamins, polyunsaturated fatty acids, bioactive components. Adding complex fat globule membranes to vegetable oil-based formula has potential enhance development reduce infections. Cholesterol provision breastfeeding modulates sterol metabolism may induce long-term benefits. Some 98-99% of are comprised by triacylglycerols, whose properties depend on incorporated acids. Attention been devoted roles long-chain acids docosahexaenoic (DHA) arachidonic (ARA) Recent studies gene-diet interaction (Mendelian randomization) show that providing DHA ARA improves cognitive reduces asthma risk at school age particularly in those children a genetically determined lower activity synthesis. It appears prudent follow biological model human design as far feasible, unless conclusive evidence for suitability safety other choices is available. The recent European Union legislative stipulation high content without required deviates from this concept, such novel composition not adequately evaluated. Great future opportunities arise significant methodological progress example lipidomic analyses their bioinformatic evaluation, which should understanding biology lipids. Such knowledge might lead improved dietary advice lactating mothers well further composition.

Language: Английский

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The Role of Lipids Interacting with α-Synuclein in the Pathogenesis of Parkinson’s Disease

Journal of Parkinson s Disease, Journal Year: 2017, Volume and Issue: 7(3), P. 433 - 450

Published: June 30, 2017

␣-synuclein is a small protein abundantly expressed in the brain and mainly located synaptic terminals.The conversion of into oligomers fibrils hallmark range neurodegenerative disorders including Parkinson's disease dementia with Lewy bodies.␣-synuclein disordered solution but can adopt an ␣-helical conformation upon binding to lipid membranes.This lipid-protein interaction plays important role its proposed biological function, i.e., plasticity, also entail aggregation protein.Both chemical properties lipids lipid-to-protein-ratio have been reported modulate propensity ␣-synuclein.In this review, influence changes nature levels on vivo vitro will be discussed within common general framework.In particular, while biophysical measurements kinetic analyses time courses presence different types vesicles allow mechanistic dissection aggregation, studies cellular animal models determination associated disease.

Language: Английский

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Targeting the alternative bile acid synthetic pathway for metabolic diseases

Protein & Cell, Journal Year: 2020, Volume and Issue: 12(5), P. 411 - 425

Published: Nov. 30, 2020

Abstract The gut microbiota is profoundly involved in glucose and lipid metabolism, part by regulating bile acid (BA) metabolism affecting multiple BA-receptor signaling pathways. BAs are synthesized the liver multi-step reactions catalyzed via two distinct routes, classical pathway (producing 12α-hydroxylated primary BA, cholic acid), alternative non-12α-hydroxylated chenodeoxycholic acid). BA synthesis excretion a major of cholesterol catabolism, thus, implicated variety metabolic diseases including obesity, insulin resistance, nonalcoholic fatty disease. Additionally, both oxysterols function as molecules that activate nuclear membrane receptor-mediated pathways various tissues, glucose, homeostasis, inflammation, energy expenditure. Modulating composition to regulate an interesting novel direction for developing therapies In this review, we summarize most recent findings on role synthetic pathways, with focus pathway, which has been under-investigated, treating hyperglycemia We also discuss future perspectives develop promising pharmacological strategies targeting treatment diseases.

Language: Английский

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Physiology and Pathophysiology of Steroid Biosynthesis, Transport and Metabolism in the Human Placenta

Frontiers in Pharmacology, Journal Year: 2018, Volume and Issue: 9

Published: Sept. 12, 2018

The steroid hormones progestagens, estrogens, androgens and glucocorticoids as well their precursor cholesterol are required for successful establishment maintenance of pregnancy proper development the fetus. human placenta forms at interface maternal fetal circulation. It participates in biosynthesis metabolism steroids regulated exchange between compartment. This review outlines mechanisms placental handling compounds. Cholesterol is transported from mother to offspring involving lipoprotein receptors such low-density receptor (LDLR) scavenger class B type I (SRB1) ATP-binding cassette (ABC)-transporters, ABCA1 ABCG1. Additionally, also a progesterone estrogen synthesis. Hormone synthesis predominantly performed by members cytochrome P-450 (CYP) enzyme family including CYP11A1 or CYP19A1 hydroxysteroid dehydrogenases (HSD) 3β-HSD 17β-HSD. Placental requires delivery sulfate-conjugated molecules serum. uptake these precursors mediated solute carrier (SLC) sodium-dependent organic anion transporter (SOAT), 4 (OAT4), transporting polypeptide 2B1 (OATP2B1). Maternal-fetal glucocorticoid transport has be tightly order ensure healthy growth development. For that purpose, expresses enzymes 11β-HSD 1 2 ABCB1. article summarizes impact diverse compounds diseases on expression level activity involved transporters, receptors, metabolizing concludes regulatory changing physiological pathophysiological state barely explored. structure cellular composition barrier introduced. While production, syncytiotrophoblast have been explored decades, few information available role placental-fetal endothelial cells processes. With regard function, significant differences exist species. To further decipher physiologic pathways pathologic alterations handling, model systems mandatory.

Language: Английский

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The gut microbiota metabolite indole alleviates liver inflammation in mice

The FASEB Journal, Journal Year: 2018, Volume and Issue: 32(12), P. 6681 - 6693

Published: June 15, 2018

The gut microbiota regulates key hepatic functions, notably through the production of bacterial metabolites that are transported via portal circulation. We evaluated effects produced by from aromatic amino acids (phenylacetate, benzoate, p-cresol, and indole) on liver inflammation induced endotoxin. Precision-cut slices prepared control mice, Kupffer cell (KC)-depleted obese mice ( ob/ ob) were treated with or without LPS metabolites. observed beneficial indole dose-dependently reduced LPS-induced up-regulation proinflammatory mediators at both mRNA protein levels in precision-cut ob mice. KC depletion partly prevented antiinflammatory indole, a reduction nucleotide-binding domain leucine-rich repeat containing (NLR) family pyrin domain-containing 3 (NLRP3) pathway activation. In vivo, oral administration before an injection expression proteins NF-κB downstream gene up-regulation. Indole also alterations cholesterol metabolism transcriptional regulation associated increased 4β-hydroxycholesterol levels. summary, appears as metabolite tryptophan is able to counteract detrimental liver. could be new target develop innovative strategies decrease inflammation.-Beaumont, M., Neyrinck, A. Olivares, Rodriguez, J., de Rocca Serra, A., Roumain, Bindels, L. B., Cani, P. D., Evenepoel, P., Muccioli, G. G., Demoulin, J.-B., Delzenne, N. M. alleviates

Language: Английский

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The Role of Oxysterols in Human Cancer

Trends in Endocrinology and Metabolism, Journal Year: 2017, Volume and Issue: 28(7), P. 485 - 496

Published: April 12, 2017

Language: Английский

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RONS and Oxidative Stress: An Overview of Basic Concepts

Oxygen, Journal Year: 2022, Volume and Issue: 2(4), P. 437 - 478

Published: Oct. 10, 2022

Oxidative stress (OS) has greatly interested the research community in understanding damaging processes occurring cells. OS is triggered by an imbalance between reactive oxygen species (ROS) production and their elimination antioxidant system; however, ROS function as second messengers under physiological conditions. are produced from endogenous exogenous sources. Endogenous sources involve mitochondria, nicotinamide adenine dinucleotide phosphate hydrogen (NADPH), oxidases (NOXs), endoplasmic reticulum (ER), xanthine (XO), endothelial nitric oxide synthase (eNOs), others. In contrast, might be generated through ultraviolet (UV) light, ionizing radiation (IR), contaminants, heavy metals, among It can damage DNA, lipids, proteins if not controlled. To avoid oxidative damage, systems activated. present review, we focus on basic concepts of OS, highlighting nitrogen (RONS) derived internal external last elimination. Moreover, include cellular system regulation ability to decrease OS. External antioxidants also proposed alternatives ameliorate Finally, review diseases involving mechanisms.

Language: Английский

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Nanoparticles Containing Oxidized Cholesterol Deliver mRNA to the Liver Microenvironment at Clinically Relevant Doses

Advanced Materials, Journal Year: 2019, Volume and Issue: 31(14)

Published: Feb. 12, 2019

Abstract Using mRNA to produce therapeutic proteins is a promising approach treat genetic diseases. However, systemically delivering cell types besides hepatocytes remains challenging. Fast identification of nanoparticle delivery (FIND) DNA barcode‐based system designed measure how over 100 lipid nanoparticles (LNPs) deliver that functions in the cytoplasm target cells single mouse. By using FIND quantify 75 chemically distinct LNPs delivered 28 vivo, it found an LNP formulated with oxidized cholesterol and no targeting ligand delivers Cre mRNA, which edits hepatic endothelial Kupffer at 0.05 mg kg −1 . Notably, targets liver microenvironmental fivefold more potently than hepatocytes. The structure cholesterols added systematically varied show position oxidative modification may be important; modified on hydrocarbon tail associated sterol ring D tend outperform B. These data suggest can gene‐editing microenvironment clinically relevant doses.

Language: Английский

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7-Ketocholesterol in disease and aging

Redox Biology, Journal Year: 2019, Volume and Issue: 29, P. 101380 - 101380

Published: Nov. 14, 2019

7-Ketocholesterol (7KC) is a toxic oxysterol that associated with many diseases and disabilities of aging, as well several orphan diseases. 7KC the most common product reaction between cholesterol oxygen radicals concentrated found in blood arterial plaques coronary artery disease patients various other tissues cell types. Unlike cholesterol, consistently shows cytotoxicity to cells its physiological function humans or complex organisms unknown. Oxysterols, particularly 7KC, have also been shown diffuse through membranes where they affect receptor enzymatic function. Here, we will explore known proposed mechanisms pathologies are speculate about future diagnostic therapeutic target medicine.

Language: Английский

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