Uterine smooth muscle S-nitrosylproteome in pregnancy.
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.
Department of Pharmacology, University of Nevada School of Medicine, Reno, NV 89557, USA.
Craig
C
Ulrich
David R
DR
Quillici
Kathleen
K
Schegg
Rebekah
R
Woolsey
Akira
A
Nordmeier
Iain L O
IL
Buxton
D000818:Animals; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000737:chemistry*; D009215:Myometrium / Q000737:chemistry*; D009589:Nitrogen Oxides; D011247:Pregnancy; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000032:analysis*; D014590:Uterine Contraction
D009589:Nitrogen Oxides; D020543:Proteome