Fontes-Oliveira 2015 Abstract MiPschool London 2015

From Bioblast
Metabolic alterations in laminin Ξ±2 chain-deficient muscle cells.


Fontes-Oliveira CC, Menezes de Oliveira B, Steinz M, Schneiderat P, Durbeej M (2015)

Event: MiPschool London 2015

Congenital muscular dystrophy type 1A (MDC1A) is a severe form of muscular dystrophy caused by mutations in the gene encoding laminin Ξ±2 chain, an extracellular matrix protein[1]. MDC1A is one of the most common forms of congenital muscular dystrophy, at least in the European population. Severe phenotypic effects such as muscle hypotonia and generalized muscle weakness are observed and no curative treatment is available[1,2]. The secondary molecular mechanisms leading to muscle degeneration (muscle atrophy, apoptosis and impaired regeneration, which are features of MDC1A) are still to be elucidated[1-3]. Our group recently performed a comparative proteomic analysis of skeletal muscles from laminin Ξ±2 chain-deficient dy3K/dy3K mice, which display a complete deficiency of laminin Ξ±2 chain[4]. A large number of differentially expressed proteins in diseased compared to normal muscles were identified, and a majority of the down-regulated proteins are involved in different metabolic processes and mitochondrial metabolism[4]. Hence, we aim to further characterize metabolic alterations in MDC1A and analyze if mitochondrial dysregulation could be involved in the pathophysiological features of human MDC1A muscle cells in vitro. Skeletal muscle cells from several MDC1A patients and control subjects were utilized in this study. We performed expression analysis of several genes related to energy production.

Decreased expression of genes related to mitochondrial biogenesis and glucose metabolism were observed in human MDC1A myotubes compared to control. We also analyzed the mitochondrial membrane potential in myotubes from MDC1A patients and found increased depolarization, which suggests an impairment of mitochondrial function. Our data demonstrated that metabolic alterations could be an important feature in MDC1A. Further studies are being performed in order to characterize the metabolic profile in muscle cells from MDC1A patients.

β€’ Keywords: Congenital muscular dystrophy, Skeletal muscle, Metabolism

Labels: MiParea: Patients 

Organism: Mouse  Tissue;cell: Skeletal muscle 


1-Muscle Biol Unit, Dept Experim Med Sc, Lund Univ, Lund, Sweden. - [email protected] 2-Friedrich-Baur-Inst, Dept Neurol, Ludwig-Maximilians-Univ Munich, Germany

References and Support

Anna-Greta Crafoord Foundation. Muscle Tissue Culture Collection (MTCC), German network on muscular dystrophies (MD-NET) and German network for mitochondrial disorders (mitoNET, project D2, 01GM1113A).

  1. Voit T, TomΓ© FS (2004) The congenital muscular dystrophies. In Engel AG, Franzini- Armstrong C (eds.) Myology 3:1203-12.
  2. Gawlik KI, Durbeej M (2011) Skeletal muscle laminin and MDC1A: pathogenesis and treatment strategies. Skelet Muscle 1:9. doi: 10.1186/2044-5040-1-9.
  3. Kuang W, Xu H, Vilquin JT, Engvall E (1999) Activation of the lama2 gene in muscle regeneration: abortive regeneration in laminin alpha2-deficiency. Lab Invest 79:1601-13.
  4. de Oliveira BM, Matsumura CY, Fontes-Oliveira CC, Gawlik KI, Acosta H, Wernhoff P, Durbeej M (2014) Quantitative proteomic analysis reveals metabolic alterations, calcium dysregulation, and increased expression of extracellular matrix proteins in laminin Ξ±2 chain-deficient muscle. Mol Cell Proteomics 13:3001-13.
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