[Clinical relevance of myosin isoforms in the diaphragm].
The diaphragm as a striated muscle is characterized by the repetition of a single element arranged in series: the sarcomere containing two kinds of myofilaments: a thick one constituted by the myosin, and a thin one primarily composed of actin. The myosin molecule consists of two heads where two myosin heavy chains (MHC) are fixed, a flexible hinge with two light (MLC) chains, and long rod-shaped tails. The diaphragm contains 4 MHC isoforms (MHC-slow, MHC-2A, MHC-2B, MHC-2X) and 6 MLC isoforms (MLC-1f, MLC-3f, MLC-1sa, MLC-1sb, MLC-2f, MLC-2s/v). In humans, the diaphragm contains mainly fibers expressing the isoforms MHC-slow, MHC-2A, and MLC-2f, MLC-2s et MLC-1f. For the mechanical properties of the different isoforms, there is a gradient from the MHC-slow to the MHC-2A, MHC-2B and MHC-2X/2B. According to the circumstances, the diaphragm will adapt towards a slow profile (COPD, cardiac failure and in animals: Duchenne muscular dystrophy, denervation-1 week, age-female, corticosteroids, chronic stimulation), or a fast profile (in animals: chronic hypoxia, denervation-2 weeks, age-males) or a more oxidative profile (in animals: cachexia, obesity). The reasons why the diaphragm adapts towards a slower or a faster muscle are not known. In fact, for a given pathological situation, several factors are able to influence the fiber composition of the diaphragm. Therefore, the net result of the influence of these different factors in terms of MHC and MLC diaphragm adaptation is difficult to predict.
Labo Ademspieren, Laboratoire de Pneumologie, Onderwijs en Navorsing, Leuven, Belgique.
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D000222:Adaptation, Physiological; D000375:Aging / Q000502:physiology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002100:Cachexia / Q000378:metabolism; D003964:Diaphragm / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000378:metabolism*; D015394:Molecular Structure; D018485:Muscle Fibers, Skeletal / Q000737:chemistry; D009136:Muscular Dystrophies / Q000378:metabolism*; D018995:Myosin Heavy Chains; D018994:Myosin Light Chains; D009218:Myosins / Q000737:chemistry*; D020033:Protein Isoforms; D013256:Steroids
D000893:Anti-Inflammatory Agents; D018994:Myosin Light Chains; D020033:Protein Isoforms; D013256:Steroids; D018995:Myosin Heavy Chains; D009218:Myosins