Murphy, Sandra and Zweyer, Margit and Mundegar, Rustam R. and Swandulla, Dieter and Ohlendieck, Kay
(2018)
Proteomic identification of elevated saliva kallikrein levels in the mdx-4cv
mouse model of Duchenne muscular dystrophy.
Biochemistry and Biophysics Reports, 18 (100541).
ISSN 2405-5808
Abstract
Dystrophinopathies are multi-system disorders that affect the skeletal musculature, the cardio-respiratory system
and the central nervous system. The systematic screening of suitable biofluids for released or altered proteins
promises new insights into the highly complex pathophysiology of X-linked muscular dystrophy. However,
standard detection approaches using antibody-based assays often fail to reproducibly detect low-abundance
protein isoforms in dilute biological fluids. In contrast, mass spectrometric screening approaches enable the
proteome-wide identification of minor protein changes in biofluids. This report describes the findings from the
comparative proteomic analysis of whole saliva samples from wild type versus the established mdx-4cv mouse
model of highly progressive muscular dystrophy, focusing on the kallikrein protein family. Kallikrein-1 (Klk1)
and 13 Klk1-related peptidases were identified in saliva and serum from normal mice. Comparative proteomics
revealed elevated saliva levels of the Klk1-related peptidases Klk1-b1, Klk1-b5 and Klk-b22, as well as an increased Klk-1 concentration, which agrees with higher Klk-1 levels in serum from mdx-4cv mice. This indicates
altered cellular signaling, extracellular matrix remodeling and an altered immune response in the mdx-4cv
mouse, and establishes liquid biopsy procedures as suitable bioanalytical tools for the systematic survey of
complex pathobiochemical changes in animal models of muscular dystrophy.
| Item Type: |
Article
|
| Keywords: |
Dystrophinopathy;
Kallikrein-1;
Kallikrein-related peptidase;
Klk;
Saliva proteomics;
X-linked muscular dystrophy; |
| Academic Unit: |
Faculty of Science and Engineering > Biology |
| Item ID: |
13139 |
| Identification Number: |
https://doi.org/10.1016/j.bbrep.2018.05.006 |
| Depositing User: |
Prof. Kay Ohlendieck
|
| Date Deposited: |
22 Jul 2020 15:24 |
| Journal or Publication Title: |
Biochemistry and Biophysics Reports |
| Publisher: |
Elsevier |
| Refereed: |
Yes |
| Funders: |
Hume scholarship (Maynooth University), Muscular Dystrophy Ireland, Health Research Board (HRB), Science Foundation Ireland (SFI) |
| URI: |
|
| Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
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