Document Detail


Hyperoxic conditions inhibit airway smooth muscle myosin phosphatase in rat pups.
MedLine Citation:
PMID:  17215435     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Paul G Smith; Albana Dreshaj; Subhendu Chaudhuri; Baran M Onder; Maroun J Mhanna; Richard J Martin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  292     ISSN:  1040-0605     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-11     Completed Date:  2007-02-09     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L68-73     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Case Western Reserve University, 11100 Euclid Ave., Cleveland, OH 44106, USA. pgs3@case.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Bronchial Hyperreactivity / enzymology,  etiology
Disease Models, Animal
Humans
Hyperoxia / enzymology*
Infant, Newborn
Muscle, Smooth / enzymology*
Myosin Light Chains / metabolism
Myosin-Light-Chain Phosphatase / antagonists & inhibitors*
Phosphorylation
Rats
Rats, Sprague-Dawley
Trachea / enzymology*
Grant Support
ID/Acronym/Agency:
HL 56470/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Myosin Light Chains; EC 3.1.3.53/Myosin-Light-Chain Phosphatase

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