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Measurement of a MMP-2 degraded Titin fragment in serum reflects changes in muscle turnover induced by atrophy

Sun, S. and Henriksen, K. and Karsdal, M. A. and Armbrecht, G. and Belavy, D. L. and Felsenberg, D. and Rittweger, J. and Wang, Y. and Zheng, Q. and Nedergaard, A. F. (2014) Measurement of a MMP-2 degraded Titin fragment in serum reflects changes in muscle turnover induced by atrophy. Experimental Gerontology, 58, pp. 83-89. Elsevier. DOI: http://dx.doi.org/10.1016/j.exger.2014.07.016 ISSN 0531-5565

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Abstract

Purpose: In this study we sought to determinewhether a Titin peptide fragment can serve as a clinical biomarker for changes in muscle mass. Methods: Mass spectrometry was used to identify Titin fragment in urine. An antibody against this Titin sequence was raised and used to develop a competitive ELISA assay for measurement in serum. Rat tissue extractions in the presence or absence of a series of proteases of interest were used to identify its enzymatic origin. A rat model of dexamethasone (DEX) induced muscle atrophy and a human 56-day bed rest study with and without vibration therapy were used to assess biological and clinical relevance. Results: A technically robust ELISA measuring the Titin fragment was developed against a Titin peptide fragment identified in human urine. The fragment was shown to be produced primarily byMMP-2 cleavage of Titin. In the rat muscle DEX induced atrophy model, Titin-MMP2 fragmentwas decreased in the beginning of DEX treatment, and then significantly increased later on during DEX administration. In the human bed rest study, the Titin- MMP2 fragment was initially decreased 11.9 (±3.7) % after 1 day of bed rest, and then gradually increased ending up at a 16.4 (±4.6) % increase at day 47. Conclusions: We developed a robust ELISA measuring a muscle derived MMP-2 generated Titin degradation fragment in rat and human serum. Importantly, the fragment can be measured in serum and that these levels are related to induction of skeletal muscle atrophy.

Item URL in elib:https://elib.dlr.de/93363/
Document Type:Article
Title:Measurement of a MMP-2 degraded Titin fragment in serum reflects changes in muscle turnover induced by atrophy
Authors:
AuthorsInstitution or Email of AuthorsAuthors ORCID iD
Sun, S.Nordic Bioscience Biomarkers and Research, Herlev, DenmarkUNSPECIFIED
Henriksen, K.Nordic Bioscience Biomarkers and Research, Herlev, DenmarkUNSPECIFIED
Karsdal, M. A.Nordic Bioscience Biomarkers and Research, Herlev, DenmarkUNSPECIFIED
Armbrecht, G.Charité Campus Benjamin FranklinUNSPECIFIED
Belavy, D. L.Charité Campus Benjamin FranklinUNSPECIFIED
Felsenberg, D.Charité Campus Benjamin FranklinUNSPECIFIED
Rittweger, J.Institute of Aerospace Medicine, Deutsches Zentrum für Luft- und Raumfahrt, DLR e.V., Cologne, Germany and Medical Faculty, University of Cologne, Cologne, Germany; joern.rittweger (at) dlr.deUNSPECIFIED
Wang, Y.Nordic Bioscience Biomarkers and Research, Beijing, ChinaUNSPECIFIED
Zheng, Q.Nordic Bioscience Biomarkers and Research, Beijing, ChinaUNSPECIFIED
Nedergaard, A. F.Nordic Bioscience Biomarkers and Research, Herlev, DenmarkUNSPECIFIED
Date:2014
Journal or Publication Title:Experimental Gerontology
Refereed publication:Yes
Open Access:No
Gold Open Access:No
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:58
DOI :http://dx.doi.org/10.1016/j.exger.2014.07.016
Page Range:pp. 83-89
Editors:
EditorsEmail
Leeuwenburgh, ChristiaanUNSPECIFIED
Publisher:Elsevier
ISSN:0531-5565
Status:Published
Keywords:Titin, MMP-2, Muscle atrophy, Dexamethasone, Bed rest
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Forschung unter Weltraumbedingungen
DLR - Research theme (Project):R - Vorhaben Integrative Studien (old)
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Space Physiology
Deposited By: Becker, Christine
Deposited On:08 Jan 2015 14:57
Last Modified:08 Jan 2015 14:57

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