ERK1/2-mediated phosphorylation of myometrial caldesmon during pregnancy and labor

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 53; no. 1; pp. R192 - R199
• Main Authors: YUNPING LI, JE, Hyun-Dong, MALEK, Sabah, MORGAN, Kathleen G
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Physiological Society 2003
• Subjects: Biological and medical sciences; Clinical trials; Fundamental and applied biological sciences. Psychology; Hormone metabolism and regulation; Pregnancy. Parturition. Lactation; Premature labor; Vertebrates: reproduction; Parturition; Myometrium; Phosphorylation; myosin light chain phosphorylation; Calcium; Extracellular signal-regulated protein kinase; Rat; Enzyme; Transferases; Rodentia; Contractility; preterm labor; Myosin light chain; Pregnancy; Signal transduction; Vertebrata; Mammalia; Uterus; Caldesmon kinase; Female genital system; caldesmon
• ISSN: 0363-6119; 1522-1490

Departments of 1 Anesthesia and Critical Care and of 4 Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston 02215; 2 Boston Biomedical Research Institute, Watertown 02472; and 3 Newton Country Day School of the Sacred Heart, Newton, Massachusetts 02458 We used a timed-pregnant rat model to track changes in myometrial contractility during pregnancy and labor and to correlate these changes with upstream signaling events. Myometrium was harvested from CO2-euthanized rats. Although contraction amplitudes increased at 16 and 20 days of pregnancy, contraction incidence and area under the force curve were inhibited, consistent with the myometrial quiescence of pregnancy. The Ca2+ sensitivity of contraction was decreased at 20 days of pregnancy and this was partially reversed in labor. The protein content of h-caldesmon (h-CaD) was increased in pregnancy. A 40-fold increase in the signal from a phospho-CaD antibody specific for phosphorylation at an ERK1/2 site occurred during labor. ERK1/2 activation increased significantly at the onset of labor. Myosin light chain phosphorylation (LC20-P) increased significantly in labor compared with the nonpregnant state. Thus we conclude that the increase in CaD protein content during pregnancy may contribute to a suppression of the contractility of pregnant myometrium. Conversely, CaD phosphorylation, through an ERK1/2-mediated signaling pathway, as well as an increase in basal LC20-P, is suggested to contribute to the reversal of inhibition and promote contraction of the uterus during labor.