Document Detail

Thromboxane-induced actin polymerization in hypoxic pulmonary artery is independent of Rho.
MedLine Citation:
PMID:  21926266     Owner:  NLM     Status:  MEDLINE    
Actin polymerization (APM), regulated by Rho GTPases, promotes myocyte force generation. Hypoxia is known to impede postnatal disassembly of the actin cytoskeleton in pulmonary arterial (PA) myocytes. We compared basal and agonist-induced APM in myocytes from PA and descending aorta (Ao), under hypoxic and normoxic conditions. We also examined effects of thromboxane challenge on force generation and cytoskeletal assembly in resistance PA and renal arteries from neonatal swine with persistent pulmonary hypertension (PPHN) induced by 72-h normobaric hypoxia, compared with age-matched controls. Synthetic and contractile phenotype myocytes from neonatal porcine PA or Ao were grown in hypoxia (10% O(2)) or normoxia (21% O(2)) for 7 days, then challenged with 10(-6) M thromboxane mimetic U46619. F/G actin ratio was quantified by laser-scanning cytometry and by cytoskeletal fractionation. Thromboxane receptor (TP) G protein coupling was measured by immunoprecipitation and probing for Gαq, G12, or G13, RhoA activation by Rhotekin-RBD affinity precipitation, and LIM kinase (LIMK) and cofilin phosphorylation by Western blot. Isometric force to serial concentrations of U46619 was measured in muscular pulmonary and renal arteries from PPHN and control swine; APM was quantified in fixed contracted vessels. Contractile PA myocytes exhibit marked Rho-dependent APM in hypoxia, with increased active RhoA and LIMK phosphorylation. Their additional APM response to U46619 challenge is independent of RhoA, reflecting decreased TP association with G12/13 in favor of Gαq. In contrast, hypoxic contractile Ao myocytes polymerize actin modestly and depolymerize to U46619. Both basal APM and the APM response to U46619 are increased in PPHN PA. APM corresponds with increased force generation to U46619 challenge in PPHN PA but not renal arteries.
Jena Fediuk; Alexey Gutsol; Nora Nolette; Shyamala Dakshinamurti
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-09-16
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  302     ISSN:  1522-1504     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-12-20     Completed Date:  2012-02-22     Revised Date:  2012-08-30    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L13-26     Citation Subset:  IM    
Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada.
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MeSH Terms
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology*
Actin Cytoskeleton / metabolism*
Actins / metabolism
Animals, Newborn
Anoxia / metabolism,  physiopathology
Aorta, Thoracic / cytology,  drug effects,  physiology
Cell Culture Techniques
Cell Hypoxia / physiology*
Disease Models, Animal
Hypertension, Renovascular
Infant, Newborn
Laser Scanning Cytometry
Lim Kinases / metabolism
Muscle Cells* / drug effects,  metabolism
Persistent Fetal Circulation Syndrome / metabolism*
Pulmonary Artery / cytology,  drug effects,  physiology
Receptors, Thromboxane / metabolism
Renal Artery / cytology,  drug effects,  physiology
Thromboxanes / metabolism,  pharmacology
Vasoconstriction / drug effects
Vasoconstrictor Agents / pharmacology
rhoA GTP-Binding Protein / metabolism*
Reg. No./Substance:
0/Actins; 0/Receptors, Thromboxane; 0/Thromboxanes; 0/Vasoconstrictor Agents; 76898-47-0/15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; EC Kinases; EC GTP-Binding Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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