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The uterine smooth muscle S‐nitrosylproteome in pregnancy and functional effects of S‐nitrosoglutathione
Author(s) -
Ulrich Craig,
Quilici David,
Schegg Kathleen,
Buxton Iain,
Barnett Scott,
Heyman Nathanael
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.985.3
Subject(s) - myometrium , desmin , nitric oxide , myosin , s nitrosylation , cysteine , nitrosylation , pregnancy , chemistry , proteome , actin , myosin light chain kinase , microbiology and biotechnology , medicine , endocrinology , uterus , biology , biochemistry , immunohistochemistry , vimentin , genetics , enzyme
The molecular mechanisms involved in uterine quiescence during gestation and those responsible for induction of labor are not known. Nitric oxide relaxes uterine smooth muscle in a cGMP independent manner. S‐Nitrosylation, the covalent addition of an NO‐group to a cysteine thiol is a likely mechanism to explain the ability of NO to relax myometrium. For the first time we describe the myometrial S‐nitrosylproteome in pregnant and non‐pregnant guinea pig and the human labor, not in labor, and pre term laboring comprehensive proteome and S‐nitrosylproteome using multidimensional protein identification technology. 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. We also show that both myosin light regulatory polypeptide 9 and myosin light chain kinase are disparately S‐nitrosylated in the different states of pregnancy. We further describe both the S‐nitrosylation and activation of the potassium channel TREK‐1 by the NO donor S‐nitroso‐glutathione. Elucidation of the myometrial proteome and 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.