scholarly journals A mass spectrometric method for in-depth profiling of phosphoinositide regioisomers and their disease-associated regulation

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Shin Morioka ◽  
Hiroki Nakanishi ◽  
Toshiyoshi Yamamoto ◽  
Junya Hasegawa ◽  
Emi Tokuda ◽  
...  
Keyword(s):  
Membrane Lipids ◽  
Acyl Chain ◽  
Depth Profiling ◽  
Comprehensive Analysis ◽  
Spectrometric Method ◽  
Mass Spectrometric Method ◽  
Chiral Column ◽  
Acyl Chains ◽  
Cancer Tissues ◽  
Biological State

AbstractPhosphoinositides are a family of membrane lipids essential for many biological and pathological processes. Due to the existence of multiple phosphoinositide regioisomers and their low intracellular concentrations, profiling these lipids and linking a specific acyl variant to a change in biological state have been difficult. To enable the comprehensive analysis of phosphoinositide phosphorylation status and acyl chain identity, we develop PRMC-MS (Phosphoinositide Regioisomer Measurement by Chiral column chromatography and Mass Spectrometry). Using this method, we reveal a severe skewing in acyl chains in phosphoinositides in Pten-deficient prostate cancer tissues, extracellular mobilization of phosphoinositides upon expression of oncogenic PIK3CA, and a unique profile for exosomal phosphoinositides. Thus, our approach allows characterizing the dynamics of phosphoinositide acyl variants in intracellular and extracellular milieus.

scholarly journals Saturated very long chain fatty acid configures glycosphingolipid for lysosome homeostasis in long-lived C. elegans

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Feng Wang ◽  
Yuxi Dai ◽  
Xufeng Zhu ◽  
Qilong Chen ◽  
Huanhu Zhu ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Membrane Lipids ◽  
Acyl Chain ◽  
Behenic Acid ◽  
Long Chain Fatty Acid ◽  
Fatty Acid Elongase ◽  
C Elegans ◽  
Acyl Chains ◽  
Membrane Budding ◽  
Lifespan Regulation

AbstractThe contents of numerous membrane lipids change upon ageing. However, it is unknown whether and how any of these changes are causally linked to lifespan regulation. Acyl chains contribute to the functional specificity of membrane lipids. In this study, working with C. elegans, we identified an acyl chain-specific sphingolipid, C22 glucosylceramide, as a longevity metabolite. Germline deficiency, a conserved lifespan-extending paradigm, induces somatic expression of the fatty acid elongase ELO-3, and behenic acid (22:0) generated by ELO-3 is incorporated into glucosylceramide for lifespan regulation. Mechanistically, C22 glucosylceramide is required for the membrane localization of clathrin, a protein that regulates membrane budding. The reduction in C22 glucosylceramide impairs the clathrin-dependent autophagic lysosome reformation, which subsequently leads to TOR activation and longevity suppression. These findings reveal a mechanistic link between membrane lipids and ageing and suggest a model of lifespan regulation by fatty acid-mediated membrane configuration.

scholarly journals Caveolin-1 and cavin1 act synergistically to generate a unique lipid environment in caveolae

2021 ◽  
Vol 220 (3) ◽  
Author(s):  
Yong Zhou ◽  
Nicholas Ariotti ◽  
James Rae ◽  
Hong Liang ◽  
Vikas Tillu ◽  
...  
Keyword(s):  
Lipid Profile ◽  
Membrane Lipids ◽  
Acyl Chain ◽  
Vesicular Trafficking ◽  
Dynamic Simulations ◽  
Caveolin 1 ◽  
Vertebrate Cell ◽  
Lipid Sorting ◽  
Acyl Chains ◽  
Lipid Environment

Caveolae are specialized domains of the vertebrate cell surface with a well-defined morphology and crucial roles in cell migration and mechanoprotection. Unique compositions of proteins and lipids determine membrane architectures. The precise caveolar lipid profile and the roles of the major caveolar structural proteins, caveolins and cavins, in selectively sorting lipids have not been defined. Here, we used quantitative nanoscale lipid mapping together with molecular dynamic simulations to define the caveolar lipid profile. We show that caveolin-1 (CAV1) and cavin1 individually sort distinct plasma membrane lipids. Intact caveolar structures composed of both CAV1 and cavin1 further generate a unique lipid nano-environment. The caveolar lipid sorting capability includes selectivities for lipid headgroups and acyl chains. Because lipid headgroup metabolism and acyl chain remodeling are tightly regulated, this selective lipid sorting may allow caveolae to act as transit hubs to direct communications among lipid metabolism, vesicular trafficking, and signaling.

scholarly journals Mass spectrometric detection of cross-linked fatty acids formed during radical-induced lesion of lipid membranes

1989 ◽  
Vol 260 (3) ◽  
pp. 873-878 ◽  
Author(s):  
H Frank ◽  
D Thiel ◽  
J MacLeod
Keyword(s):  
Fatty Acids ◽  
Endoplasmic Reticulum ◽  
Lipid Membranes ◽  
Membrane Lipids ◽  
Mass Spectrometric ◽  
Spectrometric Method ◽  
Mass Spectrometric Method ◽  
Cell Toxicity ◽  
Significant Process

A mass spectrometric method is described for the quantitative determination of dimers of polyunsaturated fatty acids (PUFA) formed in the hepatic endoplasmic reticulum of rats upon inhalation of tetrachloromethane. The results show that dimers account for a considerable fraction of microsomal PUFA which disappear during CCl4 metabolism. Cross-linking of the membrane lipids of the endoplasmic reticulum seems to be a significant process with respect to cell toxicity.

scholarly journals Dissecting the nanoscale lipid profile of caveolae

2020 ◽  
Author(s):  
Yong Zhou ◽  
Nicholas Ariotti ◽  
James Rae ◽  
Hong Liang ◽  
Vikas Tillu ◽  
...  
Keyword(s):  
Lipid Profile ◽  
Membrane Lipids ◽  
Acyl Chain ◽  
Vesicular Trafficking ◽  
Structural Proteins ◽  
Dynamic Simulations ◽  
Vertebrate Cell ◽  
Lipid Sorting ◽  
Acyl Chains ◽  
Direct Communications

AbstractCaveolae are specialized domains of the vertebrate cell surface with a well-defined morphology and crucial roles in cell migration and mechanoprotection. Unique compositions of proteins and lipids determine membrane architectures. The precise caveolar lipid profile and the roles of the major caveolar structural proteins, caveolins and cavins, in selectively sorting lipids have not been defined. Here we used quantitative nanoscale lipid mapping together with molecular dynamic simulations to define the caveolar lipid profile. We show that caveolin1 (CAV1) and cavin1 individually sort distinct plasma membrane lipids. Intact caveolar structures composed of both CAV1 and cavin1 further generate a unique lipid nano-environment. The caveolar lipid sorting capability includes selectivities for lipid headgroups and acyl chains. Because lipid headgroup metabolism and acyl chain remodelling are tightly regulated, this selective lipid sorting may allow caveolae to act as transit hubs to direct communications among lipid metabolism, vesicular trafficking and signalling.

scholarly journals Lipid-dependent Subcellular Relocalization of the Acyl Chain Desaturase in Yeast

2002 ◽  
Vol 13 (12) ◽  
pp. 4429-4442 ◽  
Author(s):  
Verena Tatzer ◽  
Günther Zellnig ◽  
Sepp D. Kohlwein ◽  
Roger Schneiter
Keyword(s):  
Secretory Pathway ◽  
Unsaturated Fatty Acids ◽  
Membrane Lipids ◽  
Acyl Chain ◽  
Lipid Synthesis ◽  
Mitochondrial Morphology ◽  
Temperature Sensitive ◽  
Cell Periphery ◽  
Critical Determinant ◽  
Acyl Chains

The degree of acyl chain desaturation of membrane lipids is a critical determinant of membrane fluidity. Temperature-sensitive mutants of the single essential acyl chain desaturase, Ole1p, of yeast have previously been isolated in screens for mitochondrial inheritance mutants ( Stewart, L.C., and Yaffe, M.P. (1991). J. Cell Biol.115, 1249–1257 ). We now report that the mutant desaturase relocalizes from its uniform ER distribution to a more punctuate localization at the cell periphery upon inactivation of the enzyme. This relocalization takes place within minutes at nonpermissive conditions, a time scale at which mitochondrial morphology and inheritance is not yet affected. Relocalization of the desaturase is fully reversible and does not affect the steady state localization of other ER resident proteins or the kinetic and fidelity of the secretory pathway, indicating a high degree of selectivity for the desaturase. Relocalization of the desaturase is energy independent but is lipid dependent because it is rescued by supplementation with unsaturated fatty acids. Relocalization of the desaturase is also observed in cells treated with inhibitors of the enzyme, indicating that it is independent of temperature-induced alterations of the enzyme. In the absence of desaturase function, lipid synthesis continues, resulting in the generation of lipids with saturated acyl chains. A model is discussed in which the accumulation of saturated lipids in a microdomain around the desaturase could induce the observed segregation and relocalization of the enzyme.

Tandem Mass Spectrometric Evaluation of Core Structures of Aromatic Compounds after Catalytic Deoxygenation

2017 ◽  
Author(s):  
Xueming Dong
Keyword(s):  
Aromatic Compounds ◽  
Supported Catalyst ◽  
Mass Spectrometric ◽  
Spectrometric Method ◽  
Mass Spectrometric Method ◽  
Aromatic Rings ◽  
Tandem Mass Spectrometric ◽  
Catalytic Deoxygenation ◽  
Oxygen Atoms

Catalytic deoxygenation of coal enhances the stability and combustion performance of coal-derived liquids. However, determination of the selectivity of removal of oxygen atoms incorporated in or residing outside of aromatic rings is challenging. This limits the ability to evaluate the success of catalytic deoxygenation processes. A mass spectrometric method, in-source collision-activated dissociation (ISCAD), combined with high resolution product ion detection, is demonstrated to allow the determination of whether the oxygen atoms in aromatic compounds reside outside of aromatic rings or are part of the aromatic system, because alkyl chains can be removed from aromatic cores via ISCAD. Application of this method for the analysis of a subbituminous coal treated using a supported catalyst revealed that the catalytic treatment reduced the number of oxygen-containing heteroaromatic rings but not the number of oxygen atoms residing outside the aromatic rings.<br>

Tandem Mass Spectrometric Evaluation of Core Structures of Aromatic Compounds after Catalytic Deoxygenation

2017 ◽  
Author(s):  
Xueming Dong
Keyword(s):  
Aromatic Compounds ◽  
Supported Catalyst ◽  
Mass Spectrometric ◽  
Spectrometric Method ◽  
Mass Spectrometric Method ◽  
Aromatic Rings ◽  
Tandem Mass Spectrometric ◽  
Catalytic Deoxygenation ◽  
Oxygen Atoms

Catalytic deoxygenation of coal enhances the stability and combustion performance of coal-derived liquids. However, determination of the selectivity of removal of oxygen atoms incorporated in or residing outside of aromatic rings is challenging. This limits the ability to evaluate the success of catalytic deoxygenation processes. A mass spectrometric method, in-source collision-activated dissociation (ISCAD), combined with high resolution product ion detection, is demonstrated to allow the determination of whether the oxygen atoms in aromatic compounds reside outside of aromatic rings or are part of the aromatic system, because alkyl chains can be removed from aromatic cores via ISCAD. Application of this method for the analysis of a subbituminous coal treated using a supported catalyst revealed that the catalytic treatment reduced the number of oxygen-containing heteroaromatic rings but not the number of oxygen atoms residing outside the aromatic rings.<br>

scholarly journals Mass Spectrometric Calibration Procedure for Real-Time Detection of Lighter Hydrocarbons

Energies ◽  
2021 ◽  
Vol 14 (8) ◽  
pp. 2123
Author(s):  
Makuachukwu F. Mbaegbu ◽  
Puspa L. Adhikari ◽  
Ipsita Gupta ◽  
Mathew Rowe
Keyword(s):  
Real Time ◽  
Mass Spectrometer ◽  
Calibration Procedure ◽  
Mass Spectrometric ◽  
Spectrometric Method ◽  
Mass Selection ◽  
Mass Spectrometric Method ◽  
Mass Spectrometers ◽  
Drilling Rig

Determining gas compositions from live well fluids on a drilling rig is critical for real time formation evaluation. Development and utilization of a reliable mass spectrometric method to accurately characterize these live well fluids are always challenging due to lack of a robust and effectively selective instrument and procedure. The methods currently utilized need better calibration for the characterization of light hydrocarbons (C1–C6) at lower concentrations. The primary goal of this research is to develop and optimize a powerful and reliable analytical method to characterize live well fluid using a quadruple mass spectrometer (MS). The mass spectrometers currently being used in the field have issues with detection, spectra deconvolution, and quantification of analytes at lower concentrations (10–500 ppm), particularly for the lighter (<30 m/z) hydrocarbons. The objectives of the present study are thus to identify the detection issues, develop and optimize a better method, calibrate and QA/QC the MS, and validate the MS method in lab settings. In this study, we used two mass spectrometers to develop a selective and precise method to quantitatively analyze low level lighter analytes (C1–C6 hydrocarbons) with masses <75 m/z at concentrations 10–500 ppm. Our results suggest that proper mass selection like using base peaks with m/z 15, 26, 41, 43, 73, and 87, respectively, for methane, ethane, propane, butane, pentane, and hexane can help detect and accurately quantify hydrocarbons from gas streams. This optimized method in quadrupole mass spectrometer (QMS) will be invaluable for early characterization of the fluid components from a live hydrocarbon well in the field in real time.

scholarly journals Development of a mass spectrometric method to quantitate platelet activating factor in mouse urine.

1989 ◽  
Vol 30 (12) ◽  
pp. 1977-1981
Author(s):  
E Benfenati ◽  
D Macconi ◽  
M Noris ◽  
G Icardi ◽  
L Bettazzoli ◽  
...  
Keyword(s):  
Platelet Activating Factor ◽  
Mass Spectrometric ◽  
Spectrometric Method ◽  
Mass Spectrometric Method ◽  
Mouse Urine

scholarly journals Integrated lipidomics and proteomics reveal cardiolipin alterations, upregulation of HADHA and long chain fatty acids in pancreatic cancer stem cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Claudia Di Carlo ◽  
Bebiana C. Sousa ◽  
Marcello Manfredi ◽  
Jessica Brandi ◽  
Elisa Dalla Pozza ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Fatty Acid ◽  
Cancer Stem Cells ◽  
Acyl Chain ◽  
Fatty Acid Elongase ◽  
Acyl Chains ◽  
A Chain ◽  
Pancreatic Cancer Stem Cells ◽  
Long Chain

AbstractPancreatic cancer stem cells (PCSCs) play a key role in the aggressiveness of pancreatic ductal adenocarcinomas (PDAC); however, little is known about their signaling and metabolic pathways. Here we show that PCSCs have specific and common proteome and lipidome modulations. PCSCs displayed downregulation of lactate dehydrogenase A chain, and upregulation of trifunctional enzyme subunit alpha. The upregulated proteins of PCSCs are mainly involved in fatty acid (FA) elongation and biosynthesis of unsaturated FAs. Accordingly, lipidomics reveals an increase in long and very long-chain unsaturated FAs, which are products of fatty acid elongase-5 predicted as a key gene. Moreover, lipidomics showed the induction in PCSCs of molecular species of cardiolipin with mixed incorporation of 16:0, 18:1, and 18:2 acyl chains. Our data indicate a crucial role of FA elongation and alteration in cardiolipin acyl chain composition in PCSCs, representing attractive therapeutic targets in PDAC.

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