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Research ArticleArticle

Uterine Smooth Muscle S-Nitrosylproteome in Pregnancy

Craig Ulrich, David R. Quillici, Kathleen Schegg, Rebekah Woolsey, Akira Nordmeier and Iain L. O. Buxton
Molecular Pharmacology February 2012, 81 (2) 143-153; DOI: https://doi.org/10.1124/mol.111.075804
Craig Ulrich
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David R. Quillici
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Kathleen Schegg
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Rebekah Woolsey
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Akira Nordmeier
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Iain L. O. Buxton
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Abstract

The molecular mechanisms involved in uterine quiescence during gestation and those responsible for induction of labor are not completely known. Nitric oxide relaxes uterine smooth muscle in a manner disparate from that for other smooth muscles because global elevation of cGMP after activation of soluble guanylyl cyclase does not relax the muscle. S-Nitrosylation, the covalent addition of an nitric oxide (NO) group to a cysteine thiol is a likely mechanism to explain the ability of NO to relax myometrium. This work is the first to describe the myometrial S-nitrosylproteome in both pregnant and nonpregnant tissue states. Using the guinea pig model, we show that specific sets of proteins involved in contraction and relaxation are S-nitrosylated in laboring and nonlaboring muscle and that many of these proteins are uniquely S-nitrosylated in only one state of the tissue. In particular, we show that S-nitrosylation of the intermediate filament protein desmin is significantly increased (5.7-fold, p < 0.005) in pregnancy and that this increase cannot be attributed solely to the increase in protein expression (1.8-fold, p < 0.005) that accompanies pregnancy. Elucidation of the myometrial S-nitrosylproteome provides a list of mechanistically important proteins that can constitute the basis of hypotheses formed to explain the regulation of uterine contraction/relaxation.

Footnotes

  • This work was supported by the National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development [Grant R01-HD053028]; National Institutes of Health National Center for Research Resources [Grant P20-RR016464]; and a Gates Grand Challenges Grant (to I.L.O.B.).

  • Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.

    http://dx.doi.org/10.1124/mol.111.075804.

  • ABBREVIATIONS:

    USM
    uterine smooth muscle
    NO
    nitric oxide
    LY 83583
    6-anilino-5,8-quinolinedione
    NEM
    N-ethylmaleimide
    CHAPS
    3-(3-cholamidopropyl)dimethylammonio-1-propanesulfonate
    biotin-HPDP
    N-[6-(biotinamido)hexyl]-3′-(2′-pyridyldithio) propionamide
    GSNO
    S-nitroso-glutathione
    LC
    liquid chromatography
    MS/MS
    tandem mass spectrometry
    DIGE
    two-dimensional in-gel electrophoresis
    MS
    mass spectrometry
    MALDI
    matrix-assisted laser desorption ionization
    TOF/TOF
    tandem time of flight
    S/N
    signal/noise ratio
    SNO
    S-nitrosothiol
    MYLK
    myosin light chain kinase
    HSP27
    heat shock protein β-1
    IF
    intermediate filament.

  • Received September 16, 2011.
  • Accepted October 25, 2011.
  • Copyright © 2012 The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 81 (2)
Molecular Pharmacology
Vol. 81, Issue 2
1 Feb 2012
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Research ArticleArticle

Myometrial S-Nitrosylproteome in Pregnancy

Craig Ulrich, David R. Quillici, Kathleen Schegg, Rebekah Woolsey, Akira Nordmeier and Iain L. O. Buxton
Molecular Pharmacology February 1, 2012, 81 (2) 143-153; DOI: https://doi.org/10.1124/mol.111.075804

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Research ArticleArticle

Myometrial S-Nitrosylproteome in Pregnancy

Craig Ulrich, David R. Quillici, Kathleen Schegg, Rebekah Woolsey, Akira Nordmeier and Iain L. O. Buxton
Molecular Pharmacology February 1, 2012, 81 (2) 143-153; DOI: https://doi.org/10.1124/mol.111.075804
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