Browse
Submit Data
Databases
API
Help

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Metabolic Landscape of the Mouse Liver by Quantitative ³¹ P Nuclear Magnetic Resonance Analysis of the Phosphorome.

ABSTRACT:

Background and aims

The liver plays a central role in all metabolic processes in the body. However, precise characterization of liver metabolism is often obscured by its inherent complexity. Phosphorylated metabolites occupy a prominent position in all anabolic and catabolic pathways. Here, we develop a ³¹ P nuclear magnetic resonance (NMR)-based method to study the liver "phosphorome" through the simultaneous identification and quantification of multiple hydrophilic and hydrophobic phosphorylated metabolites.

Approach and results

We applied this technique to define the metabolic landscape in livers from a mouse model of the rare disease disorder congenital erythropoietic porphyria (CEP) as well as two well-known murine models of nonalcoholic steatohepatitis: one genetic, methionine adenosyltransferase 1A knockout mice, and the other dietary, mice fed a high-fat choline-deficient diet. We report alterations in the concentrations of phosphorylated metabolites that are readouts of the balance between glycolysis, gluconeogenesis, the pentose phosphate pathway, the tricarboxylic acid cycle, and oxidative phosphorylation and of phospholipid metabolism and apoptosis. Moreover, these changes correlate with the main histological features: steatosis, apoptosis, iron deposits, and fibrosis. Strikingly, treatment with the repurposed drug ciclopirox improves the phosphoromic profile of CEP mice, an effect that was mirrored by the normalization of liver histology.

Conclusions

In conclusion, these findings indicate that NMR-based phosphoromics may be used to unravel metabolic phenotypes of liver injury and to identify the mechanism of drug action.

SUBMITTER: Bernardo-Seisdedos G

PROVIDER: S-EPMC8362057 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Fast and Quantitative Phospholipidomic Analysis of SH-SY5Y Neuroblastoma Cell Cultures Using Liquid Chromatography-Tandem Mass Spectrometry and 31P Nuclear Magnetic Resonance.

Project description:Global lipid analysis still lags behind proteomics with respect to the availability of databases, experimental protocols, and specialized software. Determining the lipidome of cellular model systems in common use is of particular importance, especially when research questions involve lipids directly. In Parkinson's disease research, there is a growing awareness for the role of the biological membrane, where individual lipids may contribute to provoking α-synuclein oligomerisation and fibrillation. We present an analysis of the whole cell and plasma membrane lipid isolates of a neuroblastoma cell line, SH-SY5Y, a commonly used model system for research on this and other neurodegenerative diseases. We have used two complementary lipidomics methods. The relative quantities of PC, PE, SMs, CL, PI, PG, and PS were determined by 31P NMR. Fatty acid chain composition and their relative abundances within each phospholipid group were evaluated by liquid chromatography-tandem mass spectrometry. For this part of the analysis, we have developed and made available a set of Matlab scripts, LipMat. Our approach allowed us to observe several deviations of lipid abundances when compared to published reports regarding phospholipid analysis of cell cultures or brain matter. The most striking was the high abundance of PC (54.7 ± 1.9%) and low abundance of PE (17.8 ± 4.8%) and SMs (2.7 ± 1.2%). In addition, the observed abundance of PS was smaller than expected (4.7 ± 2.7%), similar to the observed abundance of PG (4.5 ± 1.8%). The observed fatty acid chain distribution was similar to the whole brain content with some notable differences: a higher abundance of 16:1 PC FA (17.4 ± 3.4% in PC whole cell content), lower abundance of 22:6 PE FA (15.9 ± 2.2% in plasma membrane fraction), and a complete lack of 22:6 PS FA.

| S-EPMC6921604 | biostudies-literature

In vivo 31P magnetic resonance spectroscopy study of mouse cerebral NAD content and redox state during neurodevelopment.

Project description:Nicotinamide adenine dinucleotide (NAD) is an important cofactor of energy-producing pathways. The redox ratio (NAD+/NADH) reflects the cellular oxidoreductive state. Oxidative stress and redox dysregulation have been suggested to contribute to various neurological diseases. The assessment of NAD content has been recently demonstrated in large animals and human brains by 31P magnetic resonance spectroscopy. However, its measurement in small rodents has never been attempted. The purpose of this study was to investigate, in vivo, the NAD content during mouse brain neurodevelopment. 31P-MR-spectra were acquired in the mouse brain at postnatal days P20, P40, P90 and P250 at 14.1 T using a 3D-localization sequence. High spectral quality was achieved at 14.1 T. NAD+ and NADH were quantified with mean Cramér-Rao lower bound of 10% and 14%, respectively. An increase in NAD+/NADH was observed from P20 to P250 due to a decrease in [NADH]. The intracellular pH was significantly reduced with age, while the free [Mg2+] in the brain was significantly increased. This study demonstrates for the first time the feasibility of the measurement of NAD content in vivo in mouse brains during development, which opens the prospect of longitudinally studying energy metabolism and redox dysfunction in mouse models of brain pathology.

| S-EPMC7519085 | biostudies-literature

Phosphorus-Containing Polymers as Sensitive Biocompatible Probes for 31P Magnetic Resonance.

Project description:The visualization of organs and tissues using 31P magnetic resonance (MR) imaging represents an immense challenge. This is largely due to the lack of sensitive biocompatible probes required to deliver a high-intensity MR signal that can be distinguished from the natural biological background. Synthetic water-soluble phosphorus-containing polymers appear to be suitable materials for this purpose due to their adjustable chain architecture, low toxicity, and favorable pharmacokinetics. In this work, we carried out a controlled synthesis, and compared the MR properties, of several probes consisting of highly hydrophilic phosphopolymers differing in composition, structure, and molecular weight. Based on our phantom experiments, all probes with a molecular weight of ~3-400 kg·mol-1, including linear polymers based on poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), poly(ethyl ethylenephosphate) (PEEP), and poly[bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)]phosphazene (PMEEEP) as well as star-shaped copolymers composed of PMPC arms grafted onto poly(amidoamine) dendrimer (PAMAM-g-PMPC) or cyclotriphosphazene-derived cores (CTP-g-PMPC), were readily detected using a 4.7 T MR scanner. The highest signal-to-noise ratio was achieved by the linear polymers PMPC (210) and PMEEEP (62) followed by the star polymers CTP-g-PMPC (56) and PAMAM-g-PMPC (44). The 31P T1 and T2 relaxation times for these phosphopolymers were also favorable, ranging between 1078 and 2368 and 30 and 171 ms, respectively. We contend that select phosphopolymers are suitable for use as sensitive 31P MR probes for biomedical applications.

| S-EPMC10005191 | biostudies-literature

A Mouse Holder for Awake Functional Imaging in Unanesthetized Mice: Applications in 31P Spectroscopy, Manganese-Enhanced Magnetic Resonance Imaging Studies, and Resting-State Functional Magnetic Resonance Imaging.

Project description:Anesthesia is often used in preclinical imaging studies that incorporate mouse or rat models. However, multiple reports indicate that anesthesia has significant physiological impacts. Thus, there has been great interest in performing imaging studies in awake, unanesthetized animals to obtain accurate results without the confounding physiological effects of anesthesia. Here, we describe a newly designed mouse holder that is interfaceable with existing MRI systems and enables awake in vivo mouse imaging. This holder significantly reduces head movement of the awake animal compared to previously designed holders and allows for the acquisition of improved anatomical images. In addition to applications in anatomical T2-weighted magnetic resonance imaging (MRI), we also describe applications in acquiring 31P spectra, manganese-enhanced magnetic resonance imaging (MEMRI) transport rates and resting-state functional magnetic resonance imaging (rs-fMRI) in awake animals and describe a successful conditioning paradigm for awake imaging. These data demonstrate significant differences in 31P spectra, MEMRI transport rates, and rs-fMRI connectivity between anesthetized and awake animals, emphasizing the importance of performing functional studies in unanesthetized animals. Furthermore, these studies demonstrate that the mouse holder presented here is easy to construct and use, compatible with standard Bruker systems for mouse imaging, and provides rigorous results in awake mice.

| S-EPMC9406174 | biostudies-literature

Nuclear Magnetic Resonance Studies of Bicontinuous Liquid Crystalline Phases of Cubic Symmetry: Transport Properties from 2H Nuclear Magnetic Resonance Relaxation Rates.

Project description:The ternary system didodecyltrimethylammonium bromide, 1-decanol, and water forms an extended reversed continuous phase of cubic symmetry at 25 °C. The cubic phase belongs to the space group Im3m, as shown by small-angle X-ray experiments. We present extensive deuterium NMR relaxation data from this cubic phase for 1-decanol, deuterated at the carbon adjacent to the hydroxyl carbon position. 2H spin-lattice (R1) and spin-spin (R2) relaxation rates were measured over the existence region of the cubic phase, which extends from 0.2 to 0.6 in volume fraction of the dividing bilayer surface of the cubic phase. The data are interpreted with an existing theoretical framework for NMR spin relaxation in bicontinuous cubic phases, which takes its starting point in the description of bicontinuous phases using periodic minimal surfaces. Specifically, we obtain the self-diffusion coefficient over the minimal surface in one unit cell for 1-decanol. We also present pulsed field gradient NMR-derived self-diffusion data for didodecyltrimethylammonium bromide and compare the two sets of data. The diffusion data for both components show a mild, if any, dependence on the volume fraction of the bilayer surface. Furthermore, we present diffusion data for the water component in the cubic phase. Finally, we discuss the influences of the choice of the value of the product of the deuterium quadrupole constant and the order parameter S. Within the framework of the model used to analyze the relaxation data, a value for this parameter is required. As an initial value, we rely on measurements of deuterium quadrupolar splittings from deuterated decanol in an anisotropic phase.

| S-EPMC10324400 | biostudies-literature

31P Nuclear Magnetic Resonance Spectroscopy as a Probe of Thorium-Phosphorus Bond Covalency: Correlating Phosphorus Chemical Shift to Metal-Phosphorus Bond Order.

Project description:We report the use of solution and solid-state 31P Nuclear Magnetic Resonance (NMR) spectroscopy combined with Density Functional Theory calculations to benchmark the covalency of actinide-phosphorus bonds, thus introducing 31P NMR spectroscopy to the investigation of molecular f-element chemical bond covalency. The 31P NMR data for [Th(PH2)(TrenTIPS)] (1, TrenTIPS = {N(CH2CH2NSiPri3)3}3-), [Th(PH)(TrenTIPS)][Na(12C4)2] (2, 12C4 = 12-crown-4 ether), [{Th(TrenTIPS)}2(μ-PH)] (3), and [{Th(TrenTIPS)}2(μ-P)][Na(12C4)2] (4) demonstrate a chemical shift anisotropy (CSA) ordering of (μ-P)3- > (═PH)2- > (μ-PH)2- > (-PH2)1- and for 4 the largest CSA for any bridging phosphido unit. The B3LYP functional with 50% Hartree-Fock mixing produced spin-orbit δiso values that closely match the experimental data, providing experimentally benchmarked quantification of the nature and extent of covalency in the Th-P linkages in 1-4 via Natural Bond Orbital and Natural Localized Molecular Orbital analyses. Shielding analysis revealed that the 31P δiso values are essentially only due to the nature of the Th-P bonds in 1-4, with largely invariant diamagnetic but variable paramagnetic and spin-orbit shieldings that reflect the Th-P bond multiplicities and s-orbital mediated transmission of spin-orbit effects from Th to P. This study has permitted correlation of Th-P δiso values to Mayer bond orders, revealing qualitative correlations generally, but which should be examined with respect to specific ancillary ligand families rather than generally to be quantitative, reflecting that 31P δiso values are a very sensitive reporter due to phosphorus being a soft donor that responds to the rest of the ligand field much more than stronger, harder donors like nitrogen.

| S-EPMC10571089 | biostudies-literature

Impact of cannabis use on brain metabolism using 31P and 1H magnetic resonance spectroscopy.

Project description:PurposeThis prospective cross-sectional study investigated the influence of regular cannabis use on brain metabolism in young cannabis users by using combined proton and phosphorus magnetic resonance spectroscopy.MethodsThe study was performed in 45 young cannabis users aged 18-30, who had been using cannabis on a regular basis over a period of at least 2 years and in 47 age-matched controls. We acquired 31P MRS data in different brain regions at 3T with a double-resonant 1H/31P head coil, anatomic images, and 1H MRS data with a standard 20-channel 1H head coil. Absolute concentration values of proton metabolites were obtained via calibration from tissue water as an internal reference, whereas a standard solution of 75 mmol/l KH2PO4 was used as an external reference for the calibration of phosphorus signals.ResultsWe found an overall but not statistically significant lower concentration level of several proton and phosphorus metabolites in cannabis users compared to non-users. In particular, energy-related phosphates such as adenosine triphosphate (ATP) and inorganic phosphate (Pi) were reduced in all regions under investigation. Phosphocreatine (PCr) showed lowered values mainly in the left basal ganglia and the left frontal white matter.ConclusionThe results suggest that the increased risk of functional brain disorders observed in long-term cannabis users could be caused by an impairment of the energy metabolism of the brain, but this needs to be verified in future studies.

| S-EPMC10567915 | biostudies-literature

A sex-specific metabolite identified in a marine invertebrate utilizing phosphorus-31 nuclear magnetic resonance.

Project description:Hormone level differences are generally accepted as the primary cause for sexual dimorphism in animal and human development. Levels of low molecular weight metabolites also differ between men and women in circulating amino acids, lipids and carbohydrates and within brain tissue. While investigating the metabolism of blue crab tissues using Phosphorus-31 Nuclear Magnetic Resonance, we discovered that only the male blue crab (Callinectes sapidus) contained a phosphorus compound with a chemical shift well separated from the expected phosphate compounds. Spectra obtained from male gills were readily differentiated from female gill spectra. Analysis from six years of data from male and female crabs documented that the sex-specificity of this metabolite was normal for this species. Microscopic analysis of male and female gills found no differences in their gill anatomy or the presence of parasites or bacteria that might produce this phosphorus compound. Analysis of a rare gynandromorph blue crab (laterally, half male and half female) proved that this sex-specificity was an intrinsic biochemical process and was not caused by any variations in the diet or habitat of male versus female crabs. The existence of a sex-specific metabolite is a previously unrecognized, but potentially significant biochemical phenomenon. An entire enzyme system has been synthesized and activated only in one sex. Unless blue crabs are a unique species, sex-specific metabolites are likely to be present in other animals. Would the presence or absence of a sex-specific metabolite affect an animal's development, anatomy and biochemistry?

| S-EPMC1940318 | biostudies-literature

Establishing lignin structure-upgradeability relationships using quantitative 1H-13C heteronuclear single quantum coherence nuclear magnetic resonance (HSQC-NMR) spectroscopy.

Project description:Lignin depolymerization could provide an attractive renewable aromatic feedstock for the chemical industry. Past studies have suggested that lignin structural features such as ether content are correlated to lignin's upgradeability. An obstacle to the development of a conclusive causal relationship between lignin structure and upgradeability has been the difficulty to quantitatively measure lignin structural features. Here, we demonstrated that a modified HSQC-NMR method known as HSQC0 can accurately quantify lignin functionalities in extracted lignin using several synthetic polymer models. We then prepared a range of isolated lignin samples with a wide range of ether contents (6-46%). By using a simple ether cleavage model, we were able to predict final depolymerization yields very accurately (<4% error), conclusively demonstrating the direct causal relationship between ether content and lignin activity. The accuracy of this model suggests that, unlike in native lignin, ether linkages no longer appear to be randomly distributed in isolated lignin.

| S-EPMC6836972 | biostudies-literature

Biomarker Discovery in Atherosclerotic Diseases Using Quantitative Nuclear Magnetic Resonance Metabolomics.

Project description:Despite great progress in the management of atherosclerosis (AS), its subsequent cardiovascular disease (CVD) remains the leading cause of morbidity and mortality. This is probably due to insufficient risk detection using routine lipid testing; thus, there is a need for more effective approaches relying on new biomarkers. Quantitative nuclear magnetic resonance (qNMR) metabolomics is able to phenotype holistic metabolic changes, with a unique advantage in regard to quantifying lipid-protein complexes. The rapidly increasing literature has indicated that qNMR-based lipoprotein particle number, particle size, lipid components, and some molecular metabolites can provide deeper insight into atherogenic diseases and could serve as novel promising determinants. Therefore, this article aims to offer an updated review of the qNMR biomarkers of AS and CVD found in epidemiological studies, with a special emphasis on lipoprotein-related parameters. As more researches are performed, we can envision more qNMR metabolite biomarkers being successfully translated into daily clinical practice to enhance the prevention, detection and intervention of atherosclerotic diseases.

| S-EPMC8356911 | biostudies-literature