Effects of eccentric exercise on myosin heavy chain (MHC) and creatine kinase (CK) enzyme expression on skeletal muscle of mdx mice

Abstract

Duchene Muscular Dystrophy (DMD) is a recessive degenerative disease linked to the X chromosome. DMD is a result of changes in a gene with 79 exons, localized in the region Xp21 of X chromosome. DMD is caused by the absence of the protein dystrophin, which is essential for muscle integrity. A lack of dystrophin leads to muscle weakness and progressive degeneration, and eventually to death due to respiratory failure. These alterations can be determined by changes of the amount of myosin heavy chain (MHC) in dystrophic muscles and, vital muscles as diaphragm can become fatigable. Serum dosages of the enzyme creatine kinase (CK) have shown and confirmed significant lesions in muscle tissue resulting from the disease. Eccentric exercise has been used to revert or minimize the morphological and functional alterations observed in dystrophic muscles. In this project we propose to analyze the effects of eccentric exercise over different fiber types and quantify the alterations in active force of single permeabilized fibers. Methods: Male mice (four/six weeks old) will be divided into four groups: (I) mdx sedentary; (II) mdx trained in treadmill running; (III) wild type sedentary; (IV) wild type trained in treadmill running. Each group will be further divided into two subgroups according to the training duration: 1 day and 9 days. After the training sessions, animals will be euthanized and sample of blood will be collected to creatine kinase enzyme (CK) expression. To MHC analysis fragments of skeletal muscles will be removed and submitted to electrophoresis technique. Expected Results: The eccentric exercise will be able to reestablish the MHC content of the dystrophic muscles and reduce the expression of CK when compared to the respective controls. (AU)