Contractile elements and myosin light chain phosphorylation in myometrial tissue from nonpregnant and pregnant women.

Abstract

Smooth muscle contraction is initiated primarily by an increase in intracellular Ca2", Ca2+-dependent activation of myosin light chain kinase, and phosphorylation of myosin light chain. In this investigation, we identified pregnancy-associated alterations in myosin light chain phosphorylation, force of contraction, and content of contractile proteins in human myometrium. Steady-state levels of myosin light chain phosphorylation and contractile stress were correlated positively in both tissues, but the myometrial strips from pregnant women developed more stress at any given level of myosin light chain phosphorylation. During spontaneous contractions and during conditions that favor maximal generation of stress, the rate and extent of myosin light chain phosphorylation were attenuated in myometrial strips from pregnant women. The content of myosin and actin per milligram of protein and per tissue cross-sectional area was similar between myometrium of nonpregnant and pregnant women. Although cell size was significantly increased in tissues obtained from pregnant women, the amounts of contractile proteins per cellular cross-sectional area were similar. In addition, myosin light chain kinase and phosphatase activities were similar in the two tissues. The content of caldesmon was significantly increased in myometrium of pregnant women, whereas that of calponin (a smooth muscle-specific protein associated with the thin filaments) was not different. We conclude that adaptations of human myometrium during pregnancy include (a) cellular mechanisms that preclude the development of high levels of myosin light chain phosphorylation during contraction and (b) an increase in the stress generating capacity for any given level of myosin light chain phosphorylation. (J. Clin. Invest. 1993. 92:29-37.)

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

“…Band densities were quantitated by using a phosphor imager. Consistent with a previous report where CaD levels were measured in human tissue (39), the CaD protein level is significantly increased during pregnancy in rat myometrium (Fig. 3B, n ϭ 30).…”

“…An increased protein level of CaD in term pregnant human myometrium compared with nonpregnant human myometrium has been reported (39). However, the contractile correlate of the increased CaD level has not been determined and whether CaD's inhibitory action may be reversed by ERK1/2-dependent phosphorylation in a gestation-related manner has not been explored.…”

Prostacyclin primes pregnant human myometrium for an enhanced contractile response in parturition

“…Others, including calponin and h-caldesmon, modulate the actomyosin complex (13,14). Previous studies have shown that expression levels of contractile apparatus proteins increase with pregnancy (15)(16)(17).…”

Caldesmon and the Regulation of Cytoskeletal Functions

“…By either mechanism, CaD negatively regulates the actomyosin interaction and acts as a molecular brake. 141 …”