TY - JOUR
T1 - Mass Spectrometric Analysis of Urinary N-Glycosylation Changes in Patients with Parkinson’s Disease
AU - Xu, Mingming
AU - Jin, Hong
AU - Ge, Wei
AU - Zhao, Lingbo
AU - Liu, Zhaoliang
AU - Guo, Zeyu
AU - Wu, Zhen
AU - Chen, Jing
AU - Mao, Chengjie
AU - Zhang, Xumin
AU - Liu, Chun-Feng
AU - Yang, Shuang
N1 - Publisher Copyright:
© 2023 American Chemical Society
PY - 2023/9/7
Y1 - 2023/9/7
N2 - Urine is thought to provide earlier and more sensitive molecular changes for biomarker discovery than blood. Numerous glycoproteins, peptides, and free glycans are present in urine through glomerular filtration of plasma, cell shedding, apoptosis, proteolytic cleavage, and exosome secretion. Urine biomarkers have enormous diagnostic potential, and the use of these biomarkers is a long-standing practice. The discovery of non-urological disease biomarkers from urine is also gaining attention due to its non-invasive sample collection and ease of analysis. Abnormal protein glycosylation in plasma or cerebrospinal fluid has been associated with Parkinson’s disease, however, whether urine with Parkinson’s disease has characteristic glycosylation remains to be explored. Here, we use mass spectrometry-based glycomics and glycoproteomics approaches to analyze urine samples for glycans, glycosites, and intact glycopeptides of urine samples. Reduced abundance of N-glycans was detected at the level of total glycans as well as specific glycosites of glycopeptides. The most abundant N-glycan in urine is S(6)1H5N4F1; S(6)2H5N4 and N4H4F1 are highly present in serum and urine, and 10 biantennary galactosylated N-glycans in the urine of PD patients were significantly decreased. The downregulation of sialylation may be due to the reduction of ST3GAL2. Site-specific N-glycosylation analysis revealed that AMBP, UMOD, and RNase1 have PD-specific N-glycosylation sites. GO and KEGG analysis revealed that N-glycosylation changes may provide clues to identify disease-specific glycosylation biomarkers in Parkinson’s disease.
AB - Urine is thought to provide earlier and more sensitive molecular changes for biomarker discovery than blood. Numerous glycoproteins, peptides, and free glycans are present in urine through glomerular filtration of plasma, cell shedding, apoptosis, proteolytic cleavage, and exosome secretion. Urine biomarkers have enormous diagnostic potential, and the use of these biomarkers is a long-standing practice. The discovery of non-urological disease biomarkers from urine is also gaining attention due to its non-invasive sample collection and ease of analysis. Abnormal protein glycosylation in plasma or cerebrospinal fluid has been associated with Parkinson’s disease, however, whether urine with Parkinson’s disease has characteristic glycosylation remains to be explored. Here, we use mass spectrometry-based glycomics and glycoproteomics approaches to analyze urine samples for glycans, glycosites, and intact glycopeptides of urine samples. Reduced abundance of N-glycans was detected at the level of total glycans as well as specific glycosites of glycopeptides. The most abundant N-glycan in urine is S(6)1H5N4F1; S(6)2H5N4 and N4H4F1 are highly present in serum and urine, and 10 biantennary galactosylated N-glycans in the urine of PD patients were significantly decreased. The downregulation of sialylation may be due to the reduction of ST3GAL2. Site-specific N-glycosylation analysis revealed that AMBP, UMOD, and RNase1 have PD-specific N-glycosylation sites. GO and KEGG analysis revealed that N-glycosylation changes may provide clues to identify disease-specific glycosylation biomarkers in Parkinson’s disease.
KW - Parkinson’s disease
KW - glycosylation
KW - mass spectrometry
KW - urine
UR - http://www.scopus.com/inward/record.url?scp=85171901167&partnerID=8YFLogxK
U2 - 10.1021/acschemneuro.3c00404
DO - 10.1021/acschemneuro.3c00404
M3 - Article
C2 - 37677068
SN - 1948-7193
VL - 14
SP - 3507
EP - 3517
JO - ACS Chemical Neuroscience
JF - ACS Chemical Neuroscience
IS - 18
ER -