Changes in the Expression of Renal Brush Border Membrane N-Glycome in Model Rats with Chronic Kidney Diseases.

Aiying Yu,Yehia Mechref,Mark C Wagner,Bruce A Molitoris,Shiv Pratap S Yadav,Jingfu Zhao

doi:10.3390/biom11111677

Abstract

Chronic kidney disease (CKD) is defined by a reduced renal function i.e., glomerular filtration rate (GFR), and the presence of kidney damage is determined by measurement of proteinuria or albuminuria. Albuminuria increases with age and can result from glomerular and/or proximal tubule (PT) alterations. Brush-border membranes (BBMs) on PT cells play an important role in maintaining the stability of PT functions. The PT BBM, a highly dynamic, organized, specialized membrane, contains a variety of glycoproteins required for the functions of PT. Since protein glycosylation regulates many protein functions, the alteration of glycosylation due to the glycan changes has attracted more interests for a variety of disease studies recently. In this work, liquid chromatography-tandem mass spectrometry was utilized to analyze the abundances of permethylated glycans from rats under control to mild CKD, severe CKD, and diabetic conditions. The most significant differences were observed in sialylation level with the highest present in the severe CKD and diabetic groups. Moreover, high mannose N-glycans was enriched in the CKD BBMs. Characterization of all the BBM N-glycan changes supports that these changes are likely to impact the functional properties of the dynamic PT BBM. Further, these changes may lead to the potential discovery of glycan biomarkers for improved CKD diagnosis and new avenues for therapeutic treatments.

Highlights

Glycosylation is one of the most important post-translational modifications (PTMs) of proteins, and it plays an essential role in numerous biological processes such as immune response, cell-extracellular communication, and cellular metabolism [1,2,3,4]
We focused on documenting glycomics changes in the purified Brush-border membranes (BBMs) that occur with Chronic kidney disease (CKD) and diabetes
High performance liquid chromatography (HPLC) grade methanol, acetonitrile (ACN), formic acid (FA), and HPLC water were obtained from Fisher

Summary

Introduction

Glycosylation is one of the most important post-translational modifications (PTMs) of proteins, and it plays an essential role in numerous biological processes such as immune response, cell-extracellular communication, and cellular metabolism [1,2,3,4]. The microheterogeneity of glycan structures is complex due to many features, such as various monosaccharide residue compositions and the diversity of linkages and branches This is one of the factors that causes the alteration of the glycosylation which has been associated with many diseases including cancers [1,6,7,8,9,10,11], Alzheimer’s disease [12,13], and diabetes [14,15,16]. The PTs contain two unique plasma membrane domains: an apical surface with microvilli and a basolateral domain each with distinct proteins and lipid compositions. This highly polar spatial organization is necessary for physiological functions and dependent upon the correct sorting and delivery of proteins and lipids to their respective surfaces [17,18].

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