Comprehensive metabonomic analysis of heart tissue from isoproterenol-induced myocardial infarction rat based on reversed-phase and hydrophilic interaction chromatography coupled to mass spectrometry

Sun, Limei; Liu, Jianxun; Sun, Ming‐Zhong; Liu, Lin; Miao, Lei; Ge, Zhengyan; Yang, Bin

doi:10.1002/jssc.201601013

Cited by 22 publications

(10 citation statements)

References 31 publications

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“…Increased GSSG levels were also observed by Liu and colleagues, who concluded that isoproterenol can inhibit both enzymes in the heart, leading to GSSG accumulation (Liu et al, 2013). However, Sun et al demonstrated the depletion of glutathione levels as an isoproterenol effect in rat hearts, in disagreement with was observed in the present study (Sun et al, 2017). Furthermore, the average ratio between reduced glutathione and oxidized glutathione (GSH/GSSG) under normal conditions, is 10:1 or greater, depending on the cell type, and an altered ratio is indicative of oxidative stress.…”

Section: Discussioncontrasting

confidence: 75%

Untargeted Metabolomics Studies of H9c2 Cardiac Cells Submitted to Oxidative Stress, β-Adrenergic Stimulation and Doxorubicin Treatment: Investigation of Cardiac Biomarkers

Lima

Amaral²,

Moretto³

et al. 2022

Front. Mol. Biosci.

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One of the biggest challenges in the search for more effective treatments for diseases is understanding their etiology. Cardiovascular diseases (CVD) are an important example of this, given the high number of deaths annually. Oxidative stress (the imbalance between oxidant and antioxidant species in biological system) is one of the factors responsible for CVD occurrence, demanding extensive investigation. Excess of reactive oxygen species (ROS) are primarily responsible for this condition, and clinical and scientific literature have reported a significant increase in ROS when therapeutic drugs, such as doxorubicin and isoproterenol, are administered. In this context, the aim of this study is the investigation of potential biomarkers that might be associated with oxidative stress in cardiomyocytes. For this purpose, H9c2 cardiomyocytes were submitted to oxidative stress conditions by treatment with doxorubicin (DOX), isoproterenol (ISO) and hydrogen peroxide (PER). Metabolomics analyses of the cell extract and the supernatant obtained from the culture medium were then evaluated by CE-ESI(+)-TOF-MS. Following signal processing, statistical analyses, and molecular features annotations, the results indicate changes in the aspartate, serine, pantothenic acid, glycerophosphocholine and glutathione metabolism in the cell extract.

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Section: Discussioncontrasting

confidence: 75%

Untargeted Metabolomics Studies of H9c2 Cardiac Cells Submitted to Oxidative Stress, β-Adrenergic Stimulation and Doxorubicin Treatment: Investigation of Cardiac Biomarkers

Lima

Amaral²,

Moretto³

et al. 2022

Front. Mol. Biosci.

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“…(Spagou et al 2010 ; Tang et al 2016 ). Indeed the combination of RPLC and HILIC has begun to be used as standard practice where comprehensive profiles are required (Contrepois et al 2015 ; Gika et al 2008 ; Paris et al 2016 ; Sun et al 2017 ). Other modes of separation employed in the analysis of extremely polar compounds have proven to be reliable and reproducible, but in the case of e.g., normal phase and ion-exchange chromatography, compatibility issues with mass spectrometry and electrospray ionisation, due to the solvents and additives used, have made these techniques less attractive than HILIC for high throughput metabolomic studies.…”

Section: Introductionmentioning

confidence: 99%

Development of a rapid profiling method for the analysis of polar analytes in urine using HILIC–MS and ion mobility enabled HILIC–MS

et al. 2019

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IntroductionAs large scale metabolic phenotyping is increasingly employed in preclinical studies and in the investigation of human health and disease the current LC–MS/MS profiling methodologies adopted for large sample sets can result in lengthy analysis times, putting strain on available resources. As a result of these pressures rapid methods of untargeted analysis may have value where large numbers of samples require screening.ObjectivesTo develop, characterise and evaluate a rapid UHP-HILIC-MS-based method for the analysis of polar metabolites in rat urine and then extend the capabilities of this approach by the addition of IMS to the system.MethodsA rapid untargeted HILIC LC–MS/MS profiling method for the analysis of small polar molecules has been developed. The 3.3 min separation used a Waters BEH amide (1 mm ID) analytical column on a Waters Synapt G2-Si Q-Tof enabled with ion mobility spectrometry (IMS). The methodology, was applied to the metabolic profiling of a series of rodent urine samples from vehicle-treated control rats and animals administered tienilic acid. The same separation was subsequently linked to IMS and MS to evaluate the benefits that IMS might provide for metabolome characterisation.ResultsThe rapid HILIC–MS method was successfully applied to rapid analysis of rat urine and found, based on the data generated from the data acquired for the pooled quality control samples analysed at regular intervals throughout the analysis, to be robust. Peak area and retention times for the compounds detected in these samples showed good reproducibility across the batch. When used to profile the urine samples obtained from vehicle-dosed control and those administered tienilic acid the HILIC-MS method detected 3007 mass/retention time features. Analysis of the same samples using HILIC–IMS–MS enabled the detection of 6711 features. Provisional metabolite identification for a number of compounds was performed using the high collision energy MS/MS information compared against the Metlin MS/MS database and, in addition, both calculated and measured CCS values from an experimentally derived CCS database.ConclusionA rapid metabolic profiling method for the analysis of polar metabolites has been developed. The method has the advantages of speed and both reducing sample and solvent consumption compared to conventional profiling methods. The addition of IMS added an additional dimension for feature detection and the identification of metabolites.Electronic supplementary materialThe online version of this article (10.1007/s11306-019-1474-9) contains supplementary material, which is available to authorized users.

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“…The significant increase in dhSPh measured by LC/MS was strongly supported by the heightened SPT activity of chorionic arteries of PE patients. Increased dhSph levels have been associated with cellular lipotoxicity, in the context of diabetes and neurodegenerative and cardiovascular diseases [47][48][49], and most likely also contributes to the onset of the endothelial dysfunction of the chorionic arteries.…”

Section: Discussionmentioning

confidence: 99%

Sphingolipid Signature of Human Feto-Placental Vasculature in Preeclampsia

Gaudio

Sasset

Lorenzo

et al. 2020

IJMS

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Bioactive sphingolipids are emerging as key regulators of vascular function and homeostasis. While most of the clinical studies have been devoted to profile circulating sphingolipids in maternal plasma, little is known about the role of the sphingolipid at the feto-placental vasculature, which is in direct contact with the offspring circulation. Our study aims to compare the sphingolipid profile of normal with preeclamptic (PE) placental chorionic arteries and isolated endothelial cells, with the goal of unveiling potential underlying pathomechanisms in the vasculature. Dihydrosphingosine and sphingomyelin (SM) concentrations (C16:0-, C18:0-, and C24:0- sphingomyelin) were significantly increased in chorionic arteries of preeclamptic placentas, whereas total ceramide, although showing a downward trend, were not statistically different. Moreover, RNA and immunofluorescence analysis showed impaired sphingosine-1-phosphate (S1P) synthesis and signaling in PE vessels. Our data reveal that the exposure to a deranged maternal intrauterine environment during PE alters the sphingolipid signature and gene expression on the fetal side of the placental vasculature. This pathological remodeling consists in increased serine palmitoyltransferase (SPT) activity and SM accrual in PE chorionic arteries, with concomitance impairment endothelial S1P signaling in the endothelium of these vessels. The increase of endothelial S1P phosphatase, lyase and S1PR2, and blunted S1PR1 expression support the onset of the pathological phenotype in chorionic arteries.

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Comprehensive metabonomic analysis of heart tissue from isoproterenol-induced myocardial infarction rat based on reversed-phase and hydrophilic interaction chromatography coupled to mass spectrometry

Cited by 22 publications

References 31 publications

Untargeted Metabolomics Studies of H9c2 Cardiac Cells Submitted to Oxidative Stress, β-Adrenergic Stimulation and Doxorubicin Treatment: Investigation of Cardiac Biomarkers

Untargeted Metabolomics Studies of H9c2 Cardiac Cells Submitted to Oxidative Stress, β-Adrenergic Stimulation and Doxorubicin Treatment: Investigation of Cardiac Biomarkers

Development of a rapid profiling method for the analysis of polar analytes in urine using HILIC–MS and ion mobility enabled HILIC–MS

Sphingolipid Signature of Human Feto-Placental Vasculature in Preeclampsia

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