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Hyperoxic conditions inhibit airway smooth muscle myosin phosphatase in rat pups. 2007

Paul G Smith, and Albana Dreshaj, and Subhendu Chaudhuri, and Baran M Onder, and Maroun J Mhanna, and Richard J Martin
Department of Pediatrics, Case Western Reserve University, 11100 Euclid Ave., Cleveland, OH 44106, USA. pgs3@case.edu

Exposure of rat pups to 100% oxygen is a model for studying neonatal lung injury. Airway reactivity is increased in this model, in part due to impaired airway smooth muscle (ASM) relaxation. We compared biochemical determinants of ASM contractility in rat pups exposed to 100% oxygen for 7 days vs. littermates raised in room air. The baseline quantities of ASM contractile proteins, extent of phosphorylation of the 20-kDa myosin regulatory light chain (LC(20)), and amount of the myosin-binding subunit of smooth muscle myosin phosphatase (MYPT) were all comparable between the two groups. Bethanechol-induced contraction increased the extent of phosphorylation of both LC(20) and MYPT in the hyperoxic group (45% and 70% over control, respectively). Relaxation after electrical field stimulation demonstrated greater phosphorylation of both LC(20) and MYPT in the hyperoxic group compared with controls (67% and 84%, respectively). To determine if hyperoxia induced changes in the isoforms of MYPT, isoform expression was also compared but differences were not found. To determine potential mechanisms whereby MYPT phosphorylation was increased by hyperoxia, separate tracheas were treated with the Rho kinase inhibitor Y-27632. This treatment completely eliminated differences in MYPT phosphorylation between the groups. Because phosphorylation of MYPT impairs the phosphatase activity of myosin phosphatase, these data suggest that hyperoxic conditioning during early postnatal life impairs relaxation through prolonging LC(20) phosphorylation. This mechanism might contribute to increased ASM reactivity seen in bronchopulmonary dysplasia.

UI MeSH Term Description Entries
D007231 Infant, Newborn An infant during the first 28 days after birth. Neonate,Newborns,Infants, Newborn,Neonates,Newborn,Newborn Infant,Newborn Infants
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000831 Animals, Newborn Refers to animals in the period of time just after birth. Animals, Neonatal,Animal, Neonatal,Animal, Newborn,Neonatal Animal,Neonatal Animals,Newborn Animal,Newborn Animals
D014132 Trachea The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. Tracheas
D016535 Bronchial Hyperreactivity Tendency of the smooth muscle of the tracheobronchial tree to contract more intensely in response to a given stimulus than it does in the response seen in normal individuals. This condition is present in virtually all symptomatic patients with asthma. The most prominent manifestation of this smooth muscle contraction is a decrease in airway caliber that can be readily measured in the pulmonary function laboratory. Bronchial Hyperreactivities,Hyperreactivities, Bronchial,Hyperreactivity, Bronchial
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats

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