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http://purl.uniprot.org/citations/25077715http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
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Purpose

In this study we sought to determine whether 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 by MMP-2 cleavage of Titin. In the rat muscle DEX induced atrophy model, Titin-MMP2 fragment was 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 1day 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."xsd:string
http://purl.uniprot.org/citations/25077715http://purl.org/dc/terms/identifier"doi:10.1016/j.exger.2014.07.016"xsd:string
http://purl.uniprot.org/citations/25077715http://purl.uniprot.org/core/author"Wang Y."xsd:string
http://purl.uniprot.org/citations/25077715http://purl.uniprot.org/core/author"Zheng Q."xsd:string
http://purl.uniprot.org/citations/25077715http://purl.uniprot.org/core/author"Sun S."xsd:string
http://purl.uniprot.org/citations/25077715http://purl.uniprot.org/core/author"Henriksen K."xsd:string
http://purl.uniprot.org/citations/25077715http://purl.uniprot.org/core/author"Armbrecht G."xsd:string
http://purl.uniprot.org/citations/25077715http://purl.uniprot.org/core/author"Felsenberg D."xsd:string
http://purl.uniprot.org/citations/25077715http://purl.uniprot.org/core/author"Karsdal M.A."xsd:string
http://purl.uniprot.org/citations/25077715http://purl.uniprot.org/core/author"Rittweger J."xsd:string
http://purl.uniprot.org/citations/25077715http://purl.uniprot.org/core/author"Belavy D.L."xsd:string
http://purl.uniprot.org/citations/25077715http://purl.uniprot.org/core/author"Nedergaard A.F."xsd:string
http://purl.uniprot.org/citations/25077715http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/25077715http://purl.uniprot.org/core/name"Exp Gerontol"xsd:string
http://purl.uniprot.org/citations/25077715http://purl.uniprot.org/core/pages"83-89"xsd:string
http://purl.uniprot.org/citations/25077715http://purl.uniprot.org/core/title"Measurement of a MMP-2 degraded Titin fragment in serum reflects changes in muscle turnover induced by atrophy."xsd:string
http://purl.uniprot.org/citations/25077715http://purl.uniprot.org/core/volume"58"xsd:string
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