Induced shift in myosin heavy chain expression in myosin myopathy by endurance training

• Published in: Journal of neurology 2004-02, Vol.251 (2), p.179-183
• Main Authors: TAJSHARGHI, Homa, STIBRANT SUNNERHAGEN, Katharina, DARIN, Niklas, KYLLERMAN, Marten, OLDFORS, Anders
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Endurance training; Exercise - physiology; Exercise Therapy; Female; Heavy chain; Humans; Isometric Contraction - genetics; Male; Medical sciences; Medicin; Middle Aged; Muscle Fibers, Fast-Twitch - cytology; Muscle Fibers, Fast-Twitch - metabolism; Muscle Fibers, Slow-Twitch - cytology; Muscle Fibers, Slow-Twitch - metabolism; Muscle Weakness - genetics; Muscle Weakness - metabolism; Muscle Weakness - rehabilitation; Muscle, Skeletal - metabolism; Muscular Diseases - genetics; Muscular Diseases - metabolism; Muscular Diseases - rehabilitation; Mutation; Mutation, Missense - genetics; Myopathy; Myosin; Myosin Heavy Chains - genetics; Myosin Heavy Chains - metabolism; Neurologi; Neurology; Physical Endurance - physiology; Physical Fitness - physiology; Protein Isoforms - genetics; Protein Isoforms - metabolism
• ISSN: 0340-5354; 1432-1459; 1432-1459
• DOI: 10.1007/s00415-004-0295-5

We recently described a new autosomal dominant myopathy (OMIM #605637) associated with a missense mutation in the myosin heavy chain (MyHC) IIa gene ( MYH2), which encodes for the fast myosin isoform that is expressed in type 2A muscle fibers. There was a correlation between muscle pathology and expression of MyHC IIa. Low expression of the mutation was associated with a milder phenotype. Since physical activity influences MyHC isoform expression in normal individuals, we investigated whether endurance training can alter the expression of MyHC isoforms in patients with the MYH2 mutation. The expression of MyHC I, IIa and IIx was analysed in muscle specimens from six patients before and after an eight-week endurancetraining program by SDS-polyacrylamide gel electrophoresis and immuno-histochemistry. There was a clear and consistent shift from fast to slow MyHC isoform expression, but the training program did not result in the desired reduction of MyHC IIa, which may be due to the limited time period of training. Fiber type transition was further illustrated by the appearance of hybrid muscle fibers expressing more than one MyHC isoform after the training period. All patients showed an increase in maximal workload but no significant change in isometric muscle strength.We conclude that endurance training in patients with myosin myopathy may be an important way to alter the expression of defective MyHC isoforms.