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Regulation of cGMP-dependent protein kinase-mediated vasodilation by hypoxia-induced reactive species in ovine fetal pulmonary veins.

Regulation of cGMP-dependent protein kinase-mediated vasodilation by hypoxia-induced reactive species in ovine fetal pulmonary veins. Research Abstract Details 

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  • Regulation of cGMP-dependent protein kinase-mediated vasodilation by hypoxia-induced reactive species in ovine fetal pulmonary veins. Abstract Text:

    sewite negashSewite Negash,yuansheng gaoYuansheng Gao,weilin zhouWeilin Zhou,jie liuJie Liu,shashi chintaShashi Chinta,j usha rajJ Usha Raj,sewite negashSewite Negash,yuansheng gaoYuansheng Gao,weilin zhouWeilin Zhou,jie liuJie Liu,shashi chintaShashi Chinta,j usha rajJ Usha Raj,

    We previously reported that hypoxia attenuates cGMP-dependent protein kinase (PKG)-mediated relaxation in pulmonary vessels (Am J Physiol Lung Cell Mol Physiol 279: L611-L618, 2003). To determine whether hypoxia-induced reactive oxygen and nitrogen species (ROS and RNS, respectively) may be involved in the downregulation of PKG-mediated relaxation, ovine fetal intrapulmonary veins were exposed to 4 h of normoxia or hypoxia, with or without scavengers of ROS [N-acetylcysteine (NAC)] or peroxynitrite (quercetin and Trolox) and preconstricted with endothelin-1. Hypoxia decreased the relaxation response to 8-bromo-cGMP, PKG protein expression, and kinase activity and increased tyrosine nitration in PKG. However, ROS and RNS scavengers prevented these changes. To determine whether increased PKG nitration diminishes PKG activity, pulmonary vein smooth muscle cells (PVSMC) were exposed to shorter-term (30 min) hypoxia, which increased PKG nitration and decreased PKG activity but did not alter PKG protein expression. Increased dihydro-2,7-dichlorofluorescein diacetate (DCFH(2)-DA) fluorescence in PVSMC after 4 h or 30 min of hypoxia was not observed in the presence of NAC, quercetin, or Trolox, suggesting increased ROS and RNS production. Increased PKG nitration and the associated decrease in PKG activity in PVSMC after 30 min of hypoxia were also reversed on reoxygenation. The consequences of PKG nitration were assessed by exposure of purified PKG-Ialpha to peroxynitrite, which caused increased 3-nitrotyrosine immunoreactivity and inhibition of kinase activity. Our data suggest that, after 30 min of hypoxia, reversible covalent modification of PKG by hypoxia-induced reactive species may be an important mechanism by which the relaxation response to cGMP is regulated. However, after 4 h of hypoxia, PKG nitration and decreased PKG expression are involved.

    Regulation of cGMP-dependent protein kinase-mediated vasodilation by hypoxia-induced reactive species in ovine fetal pulmonary veins. Publishing Authors By Initials

    s negashS Negash,y gaoY Gao,w zhouW Zhou,j liuJ Liu,s chintaS Chinta,ju rajJU Raj,s negashS Negash,y gaoY Gao,w zhouW Zhou,j liuJ Liu,s chintaS Chinta,ju rajJU Raj,

    For similar vasodilation research abstracts see: vasodilation research

    PUBMED ID PMID:

    MEDLINE DATE:

    Regulation of cGMP-dependent protein kinase-mediated vasodilation by hypoxia-induced reactive species in ovine fetal pulmonary veins. Journal Published:

    PUBLICATION TYPE: Research Support, N.I.H., Extr

    Journal: American journal of physiology. Lung cellular and

    VOLUME: 293

    Page Numbers: L1012-20

    Journal Abbreviation: Am. J. Physiol. Lung Cell Mol.

    ISSN: 1040-0605

    DAY: 6

    MONTH: 07

    YEAR: 2007

    Regulation of cGMP-dependent protein kinase-mediated vasodilation by hypoxia-induced reactive species in ovine fetal pulmonary veins. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 100901229

    Regulation of cGMP-dependent protein kinase-mediated vasodilation by hypoxia-induced reactive species in ovine fetal pulmonary veins. Keywords Mesh Terms:

    KEYWORDS: Vasodilation

    MESH TERMS: biosynthesis

    Chemical & Substance for Abstract: Regulation of cGMP-dependent protein kinase-mediated vasodilation by hypoxia-induced reactive species in ovine fetal pulmonary veins. Information

    Substance Name: cGMP-dependent protein kinase Ialpha

    Registry Number: EC 2.7.10.-

    Grant and Affiliation Information for Regulation of cGMP-dependent protein kinase-mediated vasodilation by hypoxia-induced reactive species in ovine fetal pulmonary veins.

    AFFILIATION: Division of Neonatology, Harbor-UCLA Medical Center, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles Biomedical Research Institute, Torrance, California 90502, USA. snegash@labiomed.org

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NHLBI

    GRANT: R01/MIRS HL-75187-01

    ACRONYM: HL

    MEDLINETA: Am J Physiol Lung Cell Mol Phy

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

    Number Hits: 0

    Regulation of cGMP-dependent protein kinase-mediated vasodilation by hypoxia-induced reactive species in ovine fetal pulmonary veins Related Publications

     

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