Analysis of the Site-Specific Myoglobin Modifications in the Melibiose-Derived Novel Advanced Glycation End-Product
MAGE (melibiose-derived advanced glycation end-product) is the glycation product generated in the reaction of a model protein with melibiose. The in vivo analog accumulates in several tissues; however, its origin still needs explanation. In vitro MAGE is efficiently generated under dry conditions in...
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MDPI AG
2022-10-01
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| author | Kinga Gostomska-Pampuch Jacek R. Wiśniewski Karol Sowiński Wieslaw I. Gruszecki Andrzej Gamian Magdalena Staniszewska |
| author_facet | Kinga Gostomska-Pampuch Jacek R. Wiśniewski Karol Sowiński Wieslaw I. Gruszecki Andrzej Gamian Magdalena Staniszewska |
| author_sort | Kinga Gostomska-Pampuch |
| collection | DOAJ |
| description | MAGE (melibiose-derived advanced glycation end-product) is the glycation product generated in the reaction of a model protein with melibiose. The in vivo analog accumulates in several tissues; however, its origin still needs explanation. In vitro MAGE is efficiently generated under dry conditions in contrast to the reaction carried in an aqueous solvent. Using liquid chromatography coupled with mass spectrometry, we analyzed the physicochemical properties and structures of myoglobin glycated with melibiose under different conditions. The targeted peptide analysis identified structurally different AGEs, including crosslinking and non-crosslinking modifications associated with lysine, arginine, and histidine residues. Glycation in a dry state was more efficient in the formation of structures containing an intact melibiose moiety (21.9%) compared to glycation under aqueous conditions (15.6%). The difference was reflected in characteristic fluorescence that results from protein structural changes and impact on a heme group of the model myoglobin protein. Finally, our results suggest that the formation of in vitro MAGE adduct is initiated by coupling melibiose to a model myoglobin protein. It is confirmed by the identification of intact melibiose moieties. The intermediate glycation product can further rearrange towards more advanced structures, including cross-links. This process can contribute to a pool of AGEs accumulating locally in vivo and affecting tissue biology. |
| first_indexed | 2024-03-09T19:01:54Z |
| format | Article |
| id | doaj.art-bfe9f2f1aeff40818fab67c03d5e7392 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T19:01:54Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bfe9f2f1aeff40818fab67c03d5e73922023-11-24T05:01:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123211303610.3390/ijms232113036Analysis of the Site-Specific Myoglobin Modifications in the Melibiose-Derived Novel Advanced Glycation End-ProductKinga Gostomska-Pampuch0Jacek R. Wiśniewski1Karol Sowiński2Wieslaw I. Gruszecki3Andrzej Gamian4Magdalena Staniszewska5Department of Biochemistry and Immunochemistry, Wroclaw Medical University, 50-368 Wroclaw, PolandDepartment of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, 82152 Martinsried, GermanyDepartment of Biophysics, Institute of Physics, Maria Curie-Sklodowska University, 20-031 Lublin, PolandDepartment of Biophysics, Institute of Physics, Maria Curie-Sklodowska University, 20-031 Lublin, PolandLaboratory of Medical Microbiology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, PolandFaculty of Medicine, The John Paul II Catholic University of Lublin, 20-708 Lublin, PolandMAGE (melibiose-derived advanced glycation end-product) is the glycation product generated in the reaction of a model protein with melibiose. The in vivo analog accumulates in several tissues; however, its origin still needs explanation. In vitro MAGE is efficiently generated under dry conditions in contrast to the reaction carried in an aqueous solvent. Using liquid chromatography coupled with mass spectrometry, we analyzed the physicochemical properties and structures of myoglobin glycated with melibiose under different conditions. The targeted peptide analysis identified structurally different AGEs, including crosslinking and non-crosslinking modifications associated with lysine, arginine, and histidine residues. Glycation in a dry state was more efficient in the formation of structures containing an intact melibiose moiety (21.9%) compared to glycation under aqueous conditions (15.6%). The difference was reflected in characteristic fluorescence that results from protein structural changes and impact on a heme group of the model myoglobin protein. Finally, our results suggest that the formation of in vitro MAGE adduct is initiated by coupling melibiose to a model myoglobin protein. It is confirmed by the identification of intact melibiose moieties. The intermediate glycation product can further rearrange towards more advanced structures, including cross-links. This process can contribute to a pool of AGEs accumulating locally in vivo and affecting tissue biology.https://www.mdpi.com/1422-0067/23/21/13036mass spectrometry (MS)post-translational modification (PTM)glycationmelibiose |
| spellingShingle | Kinga Gostomska-Pampuch Jacek R. Wiśniewski Karol Sowiński Wieslaw I. Gruszecki Andrzej Gamian Magdalena Staniszewska Analysis of the Site-Specific Myoglobin Modifications in the Melibiose-Derived Novel Advanced Glycation End-Product International Journal of Molecular Sciences mass spectrometry (MS) post-translational modification (PTM) glycation melibiose |
| title | Analysis of the Site-Specific Myoglobin Modifications in the Melibiose-Derived Novel Advanced Glycation End-Product |
| title_full | Analysis of the Site-Specific Myoglobin Modifications in the Melibiose-Derived Novel Advanced Glycation End-Product |
| title_fullStr | Analysis of the Site-Specific Myoglobin Modifications in the Melibiose-Derived Novel Advanced Glycation End-Product |
| title_full_unstemmed | Analysis of the Site-Specific Myoglobin Modifications in the Melibiose-Derived Novel Advanced Glycation End-Product |
| title_short | Analysis of the Site-Specific Myoglobin Modifications in the Melibiose-Derived Novel Advanced Glycation End-Product |
| title_sort | analysis of the site specific myoglobin modifications in the melibiose derived novel advanced glycation end product |
| topic | mass spectrometry (MS) post-translational modification (PTM) glycation melibiose |
| url | https://www.mdpi.com/1422-0067/23/21/13036 |
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