| Thromboxane Induced Actin Polymerization in Hypoxic Pulmonary Artery is Independent of Rho. | |
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MedLine Citation:
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PMID: 21926266 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Rationale: 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 myocytes. We compared basal and agonist-induced APM in myocytes from pulmonary artery (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 PPHN induced by 72 hour normobaric hypoxia, compared to age-matched controls. Methods: 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, probing for Gαq, G12 or G13; RhoA activation by Rhotekin-RBD affinity precipitation; 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. Results and Conclusion: 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 Gα12/13 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. |
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Authors:
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Jena Fediuk; Alexey Gutsol; Nora Nolette; Shyamala Dakshinamurti |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-9-16 |
Journal Detail:
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Title: American journal of physiology. Lung cellular and molecular physiology Volume: - ISSN: 1522-1504 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-9-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901229 Medline TA: Am J Physiol Lung Cell Mol Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1University of Manitoba. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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