Quantitative proteomic analysis reveals metabolic alterations, calcium dysregulation and increased expression of extracellular matrix proteins in laminin α2 chain-deficient muscle.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4583464
- author
- 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
- organization
- publishing date
- 2014
- 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
- pmid:24994560
- 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
- 2016-04-01 10:16:30
- date last changed
- 2022-03-27 06:42:09
@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}},
doi = {{10.1074/mcp.M113.032276}},
volume = {{13}},
year = {{2014}},
}