| Autor: |
Sarbu M; Aurel Vlaicu University of Arad , 310130 Arad, Romania.; National Institute for Research and Development in Electrochemistry and Condensed Matter, 300569 Timisoara, Romania., Robu AC; National Institute for Research and Development in Electrochemistry and Condensed Matter, 300569 Timisoara, Romania.; West University of Timisoara , 300223 Timisoara, Romania., Ghiulai RM; Department of Pharmacy, Victor Babes University of Medicine and Pharmacy , 300041 Timisoara, Romania., Vukelić Ž; Department of Chemistry and Biochemistry, University of Zagreb Medical School , HR-10000 Zagreb, Croatia., Clemmer DE; Department of Chemistry, Indiana University , Bloomington, Indiana 47405, United States., Zamfir AD; Aurel Vlaicu University of Arad , 310130 Arad, Romania.; National Institute for Research and Development in Electrochemistry and Condensed Matter, 300569 Timisoara, Romania. |
| Abstrakt: |
The progress of ion mobility spectrometry (IMS), together with its association to mass spectrometry (MS), opened new directions for the identification of various metabolites in complex biological matrices. However, glycolipidomics of the human brain by IMS MS represents an area untouched up to now, because of the difficulties encountered in brain sampling, analyte extraction, and IMS MS method optimization. In this study, IMS MS was introduced in human brain ganglioside (GG) research. The efficiency of the method in clinical glycolipidomics was demonstrated on a highly complex mixture extracted from a normal fetal frontal lobe (FL37). Using this approach, a remarkably rich molecular ion pattern was discovered, which proved the presence of a large number of glycoforms and an unpredicted diversity of the ceramide chains. Moreover, the results showed for the first time the occurrence of GGs in the human brain with a much higher degree of sialylation than previously reported. Using IMS MS, the entire series starting from mono- up to octasialylated GGs was detected in FL37. These findings substantiate early clinical reports on the direct correlation between GG sialylation degree and brain developmental stage. Using IMS CID MS/MS, applied here for the first time to gangliosides, a novel, tetrasialylated O-GalNAc modified species with a potential biomarker role in brain development was structurally characterized. Under variable collision energy, a high number of sequence ions was generated for the investigated GalNAc-GQ1(d18:1/18:0) species. Several fragment ions documented the presence of the tetrasialo element attached to the inner Gal, indicating that GalNAc-GQ1(d18:1/18:0) belongs to the d series. |
