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Contraction in Human Myometrium Is Associated with Changes in Small Heat Shock Proteins

Mothers and Babies Research Centre (D.A.M., E.K.T., M.R., R.S., E.-C.C.), The University of Newcastle, John Hunter Hospital, New Lambton Heights, Newcastle 2305, Australia; and KK Women’s and Children’s Hospital (G.Y., K.K.), Singapore 229899, Singapore

Address all correspondence and requests for reprints to: Dr. Eng-Cheng Chan, Mothers and Babies Research Centre, The University of Newcastle, John Hunter Hospital, 1 Lookout Road, New Lambton Heights, Newcastle 2305, Australia. E-mail: Cheng.Chan{at}newcastle.edu.au.

The myometrium undergoes substantial remodeling at the time of labor including rearrangement of the cellular contractile machinery. The regulation of this process in human myometrium at the time of labor is poorly defined, but evidence in other muscle types suggests modulation by small heat shock proteins (sHSP). The aim of this study was to investigate whether similar changes in sHSP occur in the myometrium at labor. Using a quantitative proteomic approach (two-dimensional difference gel electrophoresis), we found a 69% decrease in the sHSP B-crystallin in the myometrium at labor plus multiple isoforms of HSP27. Immunoblotting using phosphospecific HSP27 antibodies (HSP27-serine15, -78, and -82) detected marked changes in HSP27 phosphorylation at labor. Although total HSP27 levels were unchanged, HSP27-Ser15 was 3-fold higher at labor. Coimmunoprecipitation studies showed that HSP27 coprecipitates with B-crystallin and also smooth muscle -actin. Coimmunofluorescence studies demonstrated a relocation of HSP27 from the perinuclear region to the actin cytoskeleton at labor. The functional significance of these changes was demonstrated in vitro where myometrial strips stimulated to contract with oxytocin exhibited increased HSP27-Ser15 phosphorylation. Our findings provide data consistent with a novel pathway regulating human myometrial contraction at labor and identify HSP27 and B-crystallin as potential targets for future tocolytic design.

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