scholarly journals Gangliosides as Biomarkers of Human Brain Diseases: Trends in Discovery and Characterization by High-Performance Mass Spectrometry

2022 ◽  
Vol 23 (2) ◽  
pp. 693
Author(s):  
Mirela Sarbu ◽  
Raluca Ica ◽  
Alina D. Zamfir

Gangliosides are effective biochemical markers of brain pathologies, being also in the focus of research as potential therapeutic targets. Accurate brain ganglioside mapping is an essential requirement for correlating the specificity of their composition with a certain pathological state and establishing a well-defined set of biomarkers. Among all bioanalytical methods conceived for this purpose, mass spectrometry (MS) has developed into one of the most valuable, due to the wealth and consistency of structural information provided. In this context, the present article reviews the achievements of MS in discovery and structural analysis of gangliosides associated with severe brain pathologies. The first part is dedicated to the contributions of MS in the assessment of ganglioside composition and role in the specific neurodegenerative disorders: Alzheimer’s and Parkinson’s diseases. A large subsequent section is devoted to cephalic disorders (CD), with an emphasis on the MS of gangliosides in anencephaly, the most common and severe disease in the CD spectrum. The last part is focused on the major accomplishments of MS-based methods in the discovery of ganglioside species, which are associated with primary and secondary brain tumors and may either facilitate an early diagnosis or represent target molecules for immunotherapy oriented against brain cancers.

Toxics ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 32 ◽  
Author(s):  
Romel P. Dator ◽  
Morwena J. Solivio ◽  
Peter W. Villalta ◽  
Silvia Balbo

Human exposure to aldehydes is implicated in multiple diseases including diabetes, cardiovascular diseases, neurodegenerative disorders (i.e., Alzheimer’s and Parkinson’s Diseases), and cancer. Because these compounds are strong electrophiles, they can react with nucleophilic sites in DNA and proteins to form reversible and irreversible modifications. These modifications, if not eliminated or repaired, can lead to alteration in cellular homeostasis, cell death and ultimately contribute to disease pathogenesis. This review provides an overview of the current knowledge of the methods and applications of aldehyde exposure measurements, with a particular focus on bioanalytical and mass spectrometric techniques, including recent advances in mass spectrometry (MS)-based profiling methods for identifying potential biomarkers of aldehyde exposure. We discuss the various derivatization reagents used to capture small polar aldehydes and methods to quantify these compounds in biological matrices. In addition, we present emerging mass spectrometry-based methods, which use high-resolution accurate mass (HR/AM) analysis for characterizing carbonyl compounds and their potential applications in molecular epidemiology studies. With the availability of diverse bioanalytical methods presented here including simple and rapid techniques allowing remote monitoring of aldehydes, real-time imaging of aldehydic load in cells, advances in MS instrumentation, high performance chromatographic separation, and improved bioinformatics tools, the data acquired enable increased sensitivity for identifying specific aldehydes and new biomarkers of aldehyde exposure. Finally, the combination of these techniques with exciting new methods for single cell analysis provides the potential for detection and profiling of aldehydes at a cellular level, opening up the opportunity to minutely dissect their roles and biological consequences in cellular metabolism and diseases pathogenesis.


1989 ◽  
Vol 35 (7) ◽  
pp. 1282-1287 ◽  
Author(s):  
L D Bowers

Abstract The combination of HPLC and mass spectrometry has great promise for the toxicology laboratory. In the past five years, significant progress has been made toward producing a reliable interface for these techniques. Thermospray, liquid ion evaporation, ion-spray, and the particle beam separator are all viable "second generation" approaches with significant advantages and disadvantages. I review the operation of these interfaces with an orientation to their use in the drug analysis laboratory. Thermospray, ion-spray, and liquid ion evaporation primarily supply information about molecular mass. The benefits and limitations of using tandem mass spectrometry to obtain additional structural information will also be discussed.


2019 ◽  
Author(s):  
Baradwaj Gopal Ravi ◽  
Mary Grace E. Guardian ◽  
Rebecca Dickman ◽  
Zhen Q. Wang

AbstractPlants of the Digitalis genus contain a cocktail of cardenolides commonly prescribed to treat heart failure. Cardenolides in Digitalis extracts have been conventionally quantified by high-performance liquid chromatography yet the lack of structural information compounded with possible co-eluents renders this method insufficient for analyzing cardenolides in plants. The goal of this work is to structurally characterize cardiac glycosides in fresh-leaf extracts using liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) that provides exact masses. Fragmentation of cardenolides is featured by sequential loss of sugar units while the steroid aglycon moieties undergo stepwise elimination of hydroxyl groups, which distinguishes different aglycones. The sequence of elution follows diginatigenin→digoxigenin→gitoxigenin→gitaloxigenin→digitoxigenin for cardenolides with the same sugar units but different aglycones using a reverse-phase column. A linear range of 0.8-500 ng g−1 has been achieved for digoxigenin, β-acetyldigoxin, and digitoxigenin with limits of detection ranging from 0.09 to 0.45 ng g−1. A total of 17 cardenolides have been detected with lanatoside A, C, and E as major cardenolides in Digitalis lanata while 7 have been found in Digitalis purpurea including purpurea glycoside A, B, and E. Surprisingly, glucodigifucoside in D. lanata and verodoxin and digitoxigenin fucoside in D. purpurea have also been found as major cardenolides. As the first MS/MS-based method developed for analyzing cardenolides in plant extracts, this method serves as a foundation for complete identification and accurate quantification of cardiac glycosides, a necessary step towards understanding the biosynthesis of cardenolide in plants.


2005 ◽  
Vol 11 (1) ◽  
pp. 93-101 ◽  
Author(s):  
Qingrong Liang ◽  
He Qian ◽  
Weirong Yao

Identification of flavonoids and flavonoid glycosides was carried out on Psidium guajava Linn leaves by means of high-performance liquid chromatography ultraviolet (HPLC-UV) analysis and HPLC mass spectrometry. By using HPLC-UV, two known phenolics (gallic acid and quercetin) and five newly reported ones (procatechuic acid, chlorogenic acid, caffeic acid, kaempferol and ferulic acid) were identified in alcohol guava leaf extract. Structural information about the compounds was obtained from the retention times, the UV spectra and mass spectra without the need to isolate the individual compounds. Two flavonoids (quercetin and kaempferol) and four flavonoid glycosides (three known components, quercetin 3-O-alpha-L-arabinoside, quercetin 3-O-beta-D-glucoside and quercetin 3-O-beta-D-galactoside, along with one novel compound, kaempferol-glycoside) and three other unknown compounds have been identified in the fractions.


Metabolites ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 327
Author(s):  
Yvonne M. Forster ◽  
Silvan Reusser ◽  
Florian Forster ◽  
Stefan Bienz ◽  
Laurent Bigler

Spider venoms are highly complex mixtures. Numerous spider venom metabolites are uniquely found in spider venoms and are of interest concerning their potential use in pharmacology, agriculture, and cosmetics. A nontargeted ultra-high performance high-resolution electrospray tandem mass spectrometry (UHPLC-HR-ESI-MS/MS) approach offers a resource-saving way for the analysis of crude spider venom. However, the identification of known as well as the structure elucidation of unknown low molecular mass spider venom compounds based on their MS/MS spectra is challenging because (1) acylpolyamine toxins are exclusively found in spider and wasp venom, (2) reference MS/MS spectra are missing in established mass spectrometry databases, and (3) trivial names for the various toxin metabolites are used in an inconsistent way in literature. Therefore, we introduce the freely accessible MS website for low molecular mass spider venom metabolites, venoMS, containing structural information, MS/MS spectra, and links to related literature. Currently the database contains the structures of 409 acylpolyamine toxins, 36 free linear polyamines, and 81 additional spider venom metabolites. Implemented into this website is a fragment ion calculator (FRIOC) that allows us to predict fragment ions of linear polyamine derivatives. With three metabolites from the venom of the spider Agelenopsis aperta, it was demonstrated how the new website can support the structural elucidation of acylpolyamines using their MS/MS spectra.


Polymers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 97
Author(s):  
Hye Hyun Yu ◽  
Jung-Ah Lim ◽  
Seung Wook Ham ◽  
Kang-Bong Lee ◽  
Yeonhee Lee

Asian lacquer is a special polymeric material tapped from lacquer trees. The tree’s sap is a complex mixture of compounds, such as catechol lipids, polysaccharides, glycoproteins, enzymes, and water. Researchers have not yet quantitatively analyzed blended lacquers. We evaluated the compositions of Japanese and Vietnamese lacquers, and blends of the two, using time-of-flight secondary ion mass spectrometry (ToF–SIMS), pyrolysis–gas chromatography/mass spectrometry (Py–GC/MS), and high-performance liquid chromatography (HPLC). ToF–SIMS provided quantitative results for blended lacquers; provided structural information on polymeric lacquer films; and indicated the presence of dimers of urushiol–urushiol, urushiol–laccol, and laccol–laccol derivatives. We used Py–GC/MS and HPLC to obtain linear calibration curves. The specific peak intensity was a linear function of the ratio of Japanese to Vietnamese lacquer in the blends. For an unknown mixture, all three techniques gave essentially the same results. These quantitative methods will be useful for improving the physical properties of polymeric lacquer films, and evaluating the lacquer quality in industry and historic conservation.


2008 ◽  
Vol 91 (5) ◽  
pp. 1218-1226 ◽  
Author(s):  
Masao Miyazaki ◽  
Azusa Yonesige ◽  
Junko Matsuda ◽  
Yasuhiro Kuroda ◽  
Naoya Kojima ◽  
...  

Abstract Direct coupling of high-performance thin-layer chromatography (HPTLC) to matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight mass spectrometry (MS) was shown to be a reliable and reproducible method to obtain structural information and fundamental properties of glycosphingolipids (GSLs).We report a protocol for the preparation of neutral GSL extracts frommouse tissues and demonstrate the applicability of HPTLC/MS to these preparations. The protocol consists of lipid extraction and ion exchange chromatography followed by a mild alkaline treatment and a reversed-phase cartridge extraction. Possible structures for each GSL are proposed based on HPTLC/MS analyses. This fast and simple method can be used to screen neutral GSL extracts obtained from tissues and cells without isolation and purification into individual GSLs.


Author(s):  
Bruno Schueler ◽  
Robert W. Odom

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) provides unique capabilities for elemental and molecular compositional analysis of a wide variety of surfaces. This relatively new technique is finding increasing applications in analyses concerned with determining the chemical composition of various polymer surfaces, identifying the composition of organic and inorganic residues on surfaces and the localization of molecular or structurally significant secondary ions signals from biological tissues. TOF-SIMS analyses are typically performed under low primary ion dose (static SIMS) conditions and hence the secondary ions formed often contain significant structural information.This paper will present an overview of current TOF-SIMS instrumentation with particular emphasis on the stigmatic imaging ion microscope developed in the authors’ laboratory. This discussion will be followed by a presentation of several useful applications of the technique for the characterization of polymer surfaces and biological tissues specimens. Particular attention in these applications will focus on how the analytical problem impacts the performance requirements of the mass spectrometer and vice-versa.


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