High-Resolution Tandem Mass Spectrometry Identifies a Particular Ganglioside Pattern in Early Diabetic Kidney Disease of Type 2 Diabetes Mellitus Patients
Considering the valuable information provided by glycosphingolipids as molecular markers and the limited data available for their detection and characterization in patients suffering from Type 2 diabetic kidney disease (DKD), we developed and implemented a superior method based on high-resolution (H...
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MDPI AG
2022-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/9/2679 |
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| author | Anca Suteanu-Simulescu Alina Diana Zamfir Raluca Ica Mirela Sarbu Cristian V. A. Munteanu Florica Gadalean Adrian Vlad Flaviu Bob Dragos Catalin Jianu Ligia Petrica |
| author_facet | Anca Suteanu-Simulescu Alina Diana Zamfir Raluca Ica Mirela Sarbu Cristian V. A. Munteanu Florica Gadalean Adrian Vlad Flaviu Bob Dragos Catalin Jianu Ligia Petrica |
| author_sort | Anca Suteanu-Simulescu |
| collection | DOAJ |
| description | Considering the valuable information provided by glycosphingolipids as molecular markers and the limited data available for their detection and characterization in patients suffering from Type 2 diabetic kidney disease (DKD), we developed and implemented a superior method based on high-resolution (HR) mass spectrometry (MS) and tandem MS (MS/MS) for the determination of gangliosides in the urine of DKD patients. This study was focused on: (i) testing of the HR MS and MS/MS feasibility and performances in mapping and sequencing of renal gangliosides in Type 2 DM patients; (ii) determination of the changes in the urine gangliosidome of DKD patients in different stages of the disease—normo-, micro-, and macroalbuminuria—in a comparative assay with healthy controls. Due to the high resolution and mass accuracy, the comparative MS screening revealed that the sialylation status of the ganglioside components; their modification by <i>O</i>-acetyl, CH<sub>3</sub>COO<sup>−</sup>, <i>O</i>-fucosyl, and <i>O</i>-GalNAc; as well as the composition of the ceramide represent possible markers for early DKD detection, the assessment of disease progression, and follow-up treatment. Moreover, structural investigation by MS/MS demonstrated that GQ1d(d18:1/18:0), GT1α(d18:1/18:0) and GT1b(d18:1/18:0) isomers are associated with macroalbuminuria, meriting further investigation in relation to their role in DKD. |
| first_indexed | 2024-03-10T03:55:10Z |
| format | Article |
| id | doaj.art-f5deab1edca84ba38c147cfb0d739fda |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T03:55:10Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-f5deab1edca84ba38c147cfb0d739fda2023-11-23T08:47:59ZengMDPI AGMolecules1420-30492022-04-01279267910.3390/molecules27092679High-Resolution Tandem Mass Spectrometry Identifies a Particular Ganglioside Pattern in Early Diabetic Kidney Disease of Type 2 Diabetes Mellitus PatientsAnca Suteanu-Simulescu0Alina Diana Zamfir1Raluca Ica2Mirela Sarbu3Cristian V. A. Munteanu4Florica Gadalean5Adrian Vlad6Flaviu Bob7Dragos Catalin Jianu8Ligia Petrica9Department of Internal Medicine II, Division of Nephrology, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, RomaniaDepartment of Condensed Matter, National Institute for Research and Development in Electrochemistry and Condensed Matter, 300569 Timisoara, RomaniaDepartment of Condensed Matter, National Institute for Research and Development in Electrochemistry and Condensed Matter, 300569 Timisoara, RomaniaDepartment of Condensed Matter, National Institute for Research and Development in Electrochemistry and Condensed Matter, 300569 Timisoara, RomaniaDepartment of Bioinformatics & Structural Biochemistry, Institute of Biochemistry, 060031 Bucharest, RomaniaDepartment of Internal Medicine II, Division of Nephrology, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, RomaniaCentre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timisoara, RomaniaDepartment of Internal Medicine II, Division of Nephrology, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, RomaniaCentre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timisoara, RomaniaDepartment of Internal Medicine II, Division of Nephrology, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, RomaniaConsidering the valuable information provided by glycosphingolipids as molecular markers and the limited data available for their detection and characterization in patients suffering from Type 2 diabetic kidney disease (DKD), we developed and implemented a superior method based on high-resolution (HR) mass spectrometry (MS) and tandem MS (MS/MS) for the determination of gangliosides in the urine of DKD patients. This study was focused on: (i) testing of the HR MS and MS/MS feasibility and performances in mapping and sequencing of renal gangliosides in Type 2 DM patients; (ii) determination of the changes in the urine gangliosidome of DKD patients in different stages of the disease—normo-, micro-, and macroalbuminuria—in a comparative assay with healthy controls. Due to the high resolution and mass accuracy, the comparative MS screening revealed that the sialylation status of the ganglioside components; their modification by <i>O</i>-acetyl, CH<sub>3</sub>COO<sup>−</sup>, <i>O</i>-fucosyl, and <i>O</i>-GalNAc; as well as the composition of the ceramide represent possible markers for early DKD detection, the assessment of disease progression, and follow-up treatment. Moreover, structural investigation by MS/MS demonstrated that GQ1d(d18:1/18:0), GT1α(d18:1/18:0) and GT1b(d18:1/18:0) isomers are associated with macroalbuminuria, meriting further investigation in relation to their role in DKD.https://www.mdpi.com/1420-3049/27/9/2679nanoelectrosprayhigh-resolution tandem mass spectrometryscreeningfragmentation analysisdiabetic kidney diseaseganglioside biomarkers |
| spellingShingle | Anca Suteanu-Simulescu Alina Diana Zamfir Raluca Ica Mirela Sarbu Cristian V. A. Munteanu Florica Gadalean Adrian Vlad Flaviu Bob Dragos Catalin Jianu Ligia Petrica High-Resolution Tandem Mass Spectrometry Identifies a Particular Ganglioside Pattern in Early Diabetic Kidney Disease of Type 2 Diabetes Mellitus Patients Molecules nanoelectrospray high-resolution tandem mass spectrometry screening fragmentation analysis diabetic kidney disease ganglioside biomarkers |
| title | High-Resolution Tandem Mass Spectrometry Identifies a Particular Ganglioside Pattern in Early Diabetic Kidney Disease of Type 2 Diabetes Mellitus Patients |
| title_full | High-Resolution Tandem Mass Spectrometry Identifies a Particular Ganglioside Pattern in Early Diabetic Kidney Disease of Type 2 Diabetes Mellitus Patients |
| title_fullStr | High-Resolution Tandem Mass Spectrometry Identifies a Particular Ganglioside Pattern in Early Diabetic Kidney Disease of Type 2 Diabetes Mellitus Patients |
| title_full_unstemmed | High-Resolution Tandem Mass Spectrometry Identifies a Particular Ganglioside Pattern in Early Diabetic Kidney Disease of Type 2 Diabetes Mellitus Patients |
| title_short | High-Resolution Tandem Mass Spectrometry Identifies a Particular Ganglioside Pattern in Early Diabetic Kidney Disease of Type 2 Diabetes Mellitus Patients |
| title_sort | high resolution tandem mass spectrometry identifies a particular ganglioside pattern in early diabetic kidney disease of type 2 diabetes mellitus patients |
| topic | nanoelectrospray high-resolution tandem mass spectrometry screening fragmentation analysis diabetic kidney disease ganglioside biomarkers |
| url | https://www.mdpi.com/1420-3049/27/9/2679 |
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