Dataset Information

Enrichment of apolipoprotein A-IV and apolipoprotein D in the HDL proteome is associated with HDL functions in diabetic kidney disease without dialysis.

ABSTRACT: BACKGROUND AND AIMS:Diabetic kidney disease (DKD) is associated with lipid derangements that worsen kidney function and enhance cardiovascular (CVD) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CVD complications, bringing up the participation of nontraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in the HDL proteome and functionality. The HDL composition, proteome, chemical modification and functionality were analyzed in nondialysis subjects with DKD categorized according to the estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER). METHODS:Individuals with DKD were divided into eGFR>?60?mL/min/1.73?m2 plus AER stages A1 and A2 (n?=?10) and eGFR?60; n?=?8). RESULTS:Targeted proteomic analyses quantified 28 proteins associated with HDL in all groups, although only 2 were more highly expressed in the eGFR

SUBMITTER: Santana MFM

PROVIDER: S-EPMC7488728 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Enrichment of apolipoprotein A-IV and apolipoprotein D in the HDL proteome is associated with HDL functions in diabetic kidney disease without dialysis.

Santana Monique F M MFM Lira Aécio L A ALA Pinto Raphael S RS Minanni Carlos A CA Silva Amanda R M ARM Sawada Maria I B A C MIBAC Nakandakare Edna R ER Correa-Giannella Maria L C MLC Queiroz Marcia S MS Ronsein Graziella E GE Passarelli Marisa M

Lipids in health and disease 20200914 1

<h4>Background and aims</h4>Diabetic kidney disease (DKD) is associated with lipid derangements that worsen kidney function and enhance cardiovascular (CVD) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CVD complications, bringing up the participation of nontraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in the HDL proteome and functionality. The HDL composition, proteome, chem ...[more]

PMID: 32921312

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Project description:BackgroundDiabetic nephropathy (DN) is a late complication in both type 1 diabetes mellitus (T1DM) and T2DM. Already at an early stage of DN morphological changes occur at the cell surface and in the extracellular matrix where the majority of the proteins carry N-linked glycosylations. These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances.MethodWe enriched for the N-glycosylated kidney proteome in db/db mice dosed with insulin or vehicle, in streptozotocin-induced (STZ) diabetic mice and healthy control mice dosed with vehicle. Glycopeptides were analyzed with label-free shotgun mass spectrometry and differential protein abundances identified in both mouse models were compared using multivariate analyses.ResultsThe majority of the N-glycosylated proteins were similarly regulated in both mouse models. However, distinct differences between the two mouse models were for example seen for integrin-β1, a protein expressed mainly in the glomeruli which abundance was increased in the STZ diabetic mice while decreased in the db/db mice and for the sodium/glucose cotransporter-1, mainly expressed in the proximal tubules which abundance was increased in the db/db mice but decreased in the STZ diabetic mice. Insulin had an effect on the level of both glomerular and tubular proteins in the db/db mice. It decreased the abundance of G-protein coupled receptor-116 and of tyrosine-protein phosphatase non-receptor type substrate-1 away from the level in the healthy control mice.ConclusionsOur finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. Thus, N-glycosylated protein differences could be a clue to dissimilarities in T1DM and T2DM at later stages of DN. Furthermore, we observed insulin specific regulation of N-glycosylated proteins both in the direction of and away from the abundances in healthy control mice.

Dataset Information

Enrichment of apolipoprotein A-IV and apolipoprotein D in the HDL proteome is associated with HDL functions in diabetic kidney disease without dialysis.

Publications

Enrichment of apolipoprotein A-IV and apolipoprotein D in the HDL proteome is associated with HDL functions in diabetic kidney disease without dialysis.

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