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Myostatin/activin blocking combined with exercise reconditions skeletal muscle expression profile of mdx mice.
Mol Cell Endocrinol. 2015 Jan 05; 399:131-42.MC

Abstract

Duchenne muscular dystrophy is characterized by muscle wasting and decreased aerobic metabolism. Exercise and blocking of myostatin/activin signaling may independently or combined counteract muscle wasting and dystrophies. The effects of myostatin/activin blocking using soluble activin receptor-Fc (sActRIIB-Fc) administration and wheel running were tested alone or in combination for 7 weeks in dystrophic mdx mice. Expression microarray analysis revealed decreased aerobic metabolism in the gastrocnemius muscle of mdx mice compared to healthy mice. This was not due to reduced home-cage physical activity, and was further downregulated upon sActRIIB-Fc treatment in enlarged muscles. However, exercise activated pathways of aerobic metabolism and counteracted the negative effects of sActRIIB-Fc. Exercise and sActRIIB-Fc synergistically increased expression of major urinary protein, but exercise blocked sActRIIB-Fc induced phosphorylation of STAT5 in gastrocnemius muscle. In conclusion, exercise alone or in combination with myostatin/activin blocking corrects aerobic gene expression profiles of dystrophic muscle toward healthy wild type mice profiles.

Authors+Show Affiliations

Department of Biology of Physical Activity, Neuromuscular Research Center, University of Jyväskylä, Rautpohjankatu 8, P.O. Box 35, Jyväskylä FI-40014, Finland.Department of Biology of Physical Activity, Neuromuscular Research Center, University of Jyväskylä, Rautpohjankatu 8, P.O. Box 35, Jyväskylä FI-40014, Finland.Department of Biology of Physical Activity, Neuromuscular Research Center, University of Jyväskylä, Rautpohjankatu 8, P.O. Box 35, Jyväskylä FI-40014, Finland.Department of Signal Processing, Tampere University of Technology, Korkeakoulunkatu 1, P.O. BOX 553, Tampere FI-33101, Finland.Department of Biology of Physical Activity, Neuromuscular Research Center, University of Jyväskylä, Rautpohjankatu 8, P.O. Box 35, Jyväskylä FI-40014, Finland.Department of Biology of Physical Activity, Neuromuscular Research Center, University of Jyväskylä, Rautpohjankatu 8, P.O. Box 35, Jyväskylä FI-40014, Finland.Department of Medical Biochemistry and Genetics, University of Turku, Kiinamyllynkatu 10, Turku FIN-20520, Finland.Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Haartmaninkatu 3, P.O. Box 21, Helsinki FIN-00014, Finland.Department of Human Genetics, Leiden University Medical Center (LUMC), Postzone S-04-P, PO Box 9600, Leiden 2300 RC, The Netherlands.Department of Health Sciences, University of Jyväskylä, Rautpohjankatu 8, P.O. Box 35, Jyväskylä FI-40014, Finland.Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Haartmaninkatu 3, P.O. Box 21, Helsinki FIN-00014, Finland.Department of Biology of Physical Activity, Neuromuscular Research Center, University of Jyväskylä, Rautpohjankatu 8, P.O. Box 35, Jyväskylä FI-40014, Finland. Electronic address: juha.hulmi@jyu.fi.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25304272

Citation

Kainulainen, Heikki, et al. "Myostatin/activin Blocking Combined With Exercise Reconditions Skeletal Muscle Expression Profile of Mdx Mice." Molecular and Cellular Endocrinology, vol. 399, 2015, pp. 131-42.
Kainulainen H, Papaioannou KG, Silvennoinen M, et al. Myostatin/activin blocking combined with exercise reconditions skeletal muscle expression profile of mdx mice. Mol Cell Endocrinol. 2015;399:131-42.
Kainulainen, H., Papaioannou, K. G., Silvennoinen, M., Autio, R., Saarela, J., Oliveira, B. M., Nyqvist, M., Pasternack, A., 't Hoen, P. A., Kujala, U. M., Ritvos, O., & Hulmi, J. J. (2015). Myostatin/activin blocking combined with exercise reconditions skeletal muscle expression profile of mdx mice. Molecular and Cellular Endocrinology, 399, 131-42. https://doi.org/10.1016/j.mce.2014.10.001
Kainulainen H, et al. Myostatin/activin Blocking Combined With Exercise Reconditions Skeletal Muscle Expression Profile of Mdx Mice. Mol Cell Endocrinol. 2015 Jan 5;399:131-42. PubMed PMID: 25304272.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Myostatin/activin blocking combined with exercise reconditions skeletal muscle expression profile of mdx mice. AU - Kainulainen,Heikki, AU - Papaioannou,Konstantinos G, AU - Silvennoinen,Mika, AU - Autio,Reija, AU - Saarela,Janne, AU - Oliveira,Bernardo M, AU - Nyqvist,Miro, AU - Pasternack,Arja, AU - 't Hoen,Peter A C, AU - Kujala,Urho M, AU - Ritvos,Olli, AU - Hulmi,Juha J, Y1 - 2014/10/07/ PY - 2014/06/18/received PY - 2014/09/23/revised PY - 2014/10/01/accepted PY - 2014/10/12/entrez PY - 2014/10/12/pubmed PY - 2015/8/6/medline KW - Muscle hypertrophy KW - Muscular dystrophy KW - Oxidative metabolism KW - Physical activity KW - mRNA profiling SP - 131 EP - 42 JF - Molecular and cellular endocrinology JO - Mol. Cell. Endocrinol. VL - 399 N2 - Duchenne muscular dystrophy is characterized by muscle wasting and decreased aerobic metabolism. Exercise and blocking of myostatin/activin signaling may independently or combined counteract muscle wasting and dystrophies. The effects of myostatin/activin blocking using soluble activin receptor-Fc (sActRIIB-Fc) administration and wheel running were tested alone or in combination for 7 weeks in dystrophic mdx mice. Expression microarray analysis revealed decreased aerobic metabolism in the gastrocnemius muscle of mdx mice compared to healthy mice. This was not due to reduced home-cage physical activity, and was further downregulated upon sActRIIB-Fc treatment in enlarged muscles. However, exercise activated pathways of aerobic metabolism and counteracted the negative effects of sActRIIB-Fc. Exercise and sActRIIB-Fc synergistically increased expression of major urinary protein, but exercise blocked sActRIIB-Fc induced phosphorylation of STAT5 in gastrocnemius muscle. In conclusion, exercise alone or in combination with myostatin/activin blocking corrects aerobic gene expression profiles of dystrophic muscle toward healthy wild type mice profiles. SN - 1872-8057 UR - https://www.unboundmedicine.com/medline/citation/25304272/Myostatin/activin_blocking_combined_with_exercise_reconditions_skeletal_muscle_expression_profile_of_mdx_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0303-7207(14)00311-6 DB - PRIME DP - Unbound Medicine ER -