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Apoe, Mbl2 and Psp plasma protein levels correlate with diabetic phenotype in NZO mice - an optimized rapid workflow for SRM-based quantification.

J. Proteome Res. 12, 1331-1343 (2013)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Male New Zealand Obese (NZO) mice progress through pathophysiological stages similar to humans developing obesity-associated type 2 diabetes (T2D). The current challenge is to establish quantitative proteomics from small plasma sample amounts. We established an analytical workflow that facilitates a reproducible depletion of high-abundance proteins, has high throughput applicability, and allows absolute quantification of proteins from mouse plasma samples by LC-SRM-MS. The ProteoMiner equalizing technology was adjusted to the small sample amount and reproducibility of the identifications was monitored by spike proteins. Based on the label-free relative quantification of proteins in depleted plasma of a test set of NZO mice, assays for potential candidates were designed for the setup of a targeted selected reaction monitoring (SRM) approach and absolute quantification. We could demonstrate that apolipoprotein E (Apoe), mannose-binding lectin 2 (Mbl2) and parotid secretory protein (Psp) are present at significantly different quantities in depleted plasma of diabetic NZO mice compared to non-diabetic controls using AQUA peptides. Quantification was validated for Mbl2 using the ELISA technology on non-depleted plasma. We conclude that the depletion technique is applicable to restricted sample amounts and suitable for the identification of T2D signatures in plasma.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Type 2 Diabetes ; New Zealand Obese Mouse ; Proteominer ; Depletion ; Label-free Quantification ; Selected Reaction Monitoring ; Absolute Quantification ; Aqua Peptides ; Protein Signatures; New-zealand Obese ; Mannose-binding Lectin ; Parotid Secretory Protein ; Peptide Ligand Libraries ; Apolipoprotein-e ; Metabolic Syndrome ; Cell Destruction ; Innate Immunity ; Dietary-fat ; Mouse Model
Language english
Publication Year 2013
HGF-reported in Year 2013
ISSN (print) / ISBN 1535-3893
e-ISSN 1535-3907
Quellenangaben Volume: 12, Issue: 3, Pages: 1331-1343 Article Number: , Supplement: ,
Publisher American Chemical Society (ACS)
Reviewing status Peer reviewed
POF-Topic(s) 30203 - Molecular Targets and Therapies
90000 - German Center for Diabetes Research
30201 - Metabolic Health
30505 - New Technologies for Biomedical Discoveries
Research field(s) Enabling and Novel Technologies
Genetics and Epidemiology
PSP Element(s) G-505700-001
G-501900-062
G-500600-003
G-503890-001
PubMed ID 23350727
Scopus ID 84874617282
Erfassungsdatum 2013-01-28