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Quantitative proteomic analysis reveals metabolic alterations, calcium dysregulation and increased expression of extracellular matrix proteins in laminin α2 chain-deficient muscle.

Menezes de Oliveira, Bruno; Matsumura, Cintia LU ; Fontes Oliveira, Cibely LU ; Gawlik, Kinga LU ; Acosta, Helena LU ; Wernhoff, Patrik LU and Durbeej-Hjalt, Madeleine LU (2014) In Molecular & Cellular Proteomics 13(11). p.3001-3013
Abstract
Congenital muscular dystrophy with laminin α2 chain-deficiency (MDC1A) is one of the most severe forms of muscular disease and is characterized by severe muscle weakness and delayed motor milestones. The genetic basis of MDC1A is well-known, yet the secondary mechanisms ultimately leading to muscle degeneration and subsequent connective tissue infiltration are not fully understood. In order to obtain new insights into the molecular mechanisms underlying MDC1A, we performed a comparative proteomic analysis of affected muscles (diaphragm and gastrocnemius) from laminin α2 chain-deficient dy3K/dy3K mice, using the multidimensional protein identification technology combined with tandem mass tags. Out of the around 700 identified proteins, 113... (More)
Congenital muscular dystrophy with laminin α2 chain-deficiency (MDC1A) is one of the most severe forms of muscular disease and is characterized by severe muscle weakness and delayed motor milestones. The genetic basis of MDC1A is well-known, yet the secondary mechanisms ultimately leading to muscle degeneration and subsequent connective tissue infiltration are not fully understood. In order to obtain new insights into the molecular mechanisms underlying MDC1A, we performed a comparative proteomic analysis of affected muscles (diaphragm and gastrocnemius) from laminin α2 chain-deficient dy3K/dy3K mice, using the multidimensional protein identification technology combined with tandem mass tags. Out of the around 700 identified proteins, 113 and 101 proteins, respectively, were differentially expressed in the diseased gastrocnemius and diaphragm muscles compared to normal muscles. A large portion of these proteins are involved in different metabolic processes, bind calcium or are expressed in the extracellular matrix. Our findings suggest that metabolic alterations and calcium dysregulation could be novel mechanisms that underlie MDC1A and might be targets that should be explored for therapy. Also, detailed knowledge of the composition of fibrotic tissue, rich in extracellular matrix proteins, in laminin α2 chain deficient muscle may help to design future anti-fibrotic treatment. All MS data have been deposited in the ProteomeXchange with identifier PXD000978 (http://proteomecentral.proteomexchange.org/dataset/PXD000978). (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular & Cellular Proteomics
volume
13
issue
11
pages
3001 - 3013
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • pmid:24994560
  • wos:000344930500016
  • scopus:84910684594
ISSN
1535-9484
DOI
10.1074/mcp.M113.032276
language
English
LU publication?
yes
id
3ac63f64-3338-4fa4-906b-c9349e454687 (old id 4583464)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24994560?dopt=Abstract
date added to LUP
2014-08-07 00:00:14
date last changed
2017-08-20 03:10:15
@article{3ac63f64-3338-4fa4-906b-c9349e454687,
  abstract     = {Congenital muscular dystrophy with laminin α2 chain-deficiency (MDC1A) is one of the most severe forms of muscular disease and is characterized by severe muscle weakness and delayed motor milestones. The genetic basis of MDC1A is well-known, yet the secondary mechanisms ultimately leading to muscle degeneration and subsequent connective tissue infiltration are not fully understood. In order to obtain new insights into the molecular mechanisms underlying MDC1A, we performed a comparative proteomic analysis of affected muscles (diaphragm and gastrocnemius) from laminin α2 chain-deficient dy3K/dy3K mice, using the multidimensional protein identification technology combined with tandem mass tags. Out of the around 700 identified proteins, 113 and 101 proteins, respectively, were differentially expressed in the diseased gastrocnemius and diaphragm muscles compared to normal muscles. A large portion of these proteins are involved in different metabolic processes, bind calcium or are expressed in the extracellular matrix. Our findings suggest that metabolic alterations and calcium dysregulation could be novel mechanisms that underlie MDC1A and might be targets that should be explored for therapy. Also, detailed knowledge of the composition of fibrotic tissue, rich in extracellular matrix proteins, in laminin α2 chain deficient muscle may help to design future anti-fibrotic treatment. All MS data have been deposited in the ProteomeXchange with identifier PXD000978 (http://proteomecentral.proteomexchange.org/dataset/PXD000978).},
  author       = {Menezes de Oliveira, Bruno and Matsumura, Cintia and Fontes Oliveira, Cibely and Gawlik, Kinga and Acosta, Helena and Wernhoff, Patrik and Durbeej-Hjalt, Madeleine},
  issn         = {1535-9484},
  language     = {eng},
  number       = {11},
  pages        = {3001--3013},
  publisher    = {American Society for Biochemistry and Molecular Biology},
  series       = {Molecular & Cellular Proteomics},
  title        = {Quantitative proteomic analysis reveals metabolic alterations, calcium dysregulation and increased expression of extracellular matrix proteins in laminin α2 chain-deficient muscle.},
  url          = {http://dx.doi.org/10.1074/mcp.M113.032276},
  volume       = {13},
  year         = {2014},
}