Gestation Age-Related Increase in 50-kDa Rat Uterine Calcium-Independent Phospholipase A2 Expression Influences Uterine Sensitivity to Polychlorinated Biphenyl Stimulation1

Abstract

Phospholipase A2 (PLA2) enzymes catalyze the rate-limiting step in eicosanoid production by liberating arachidonic acid from membrane phospholipids. There is limited information regarding the expression pattern and activity of uterine PLA2 enzymes during pregnancy. Polychlorinated biphenyls (PCBs) are a group of persistent environmental toxicants previously associated with decreased gestation length that are capable of activating PLA2. The purpose of the present study was to determine whether uterine sensitivity to PCB stimulation is dependent on PLA2 expression, comparing rat uterine PLA2 expression in Gestational Day (gd) 10 versus gd20. Western blot analysis revealed a significant increase in the expression of calcium-dependent PLA2G2A and a 50-kDa protein immunoreactive to calcium-independent PLA2G6 antibody in gd20 compared to gd10 rat uterine tissue. The increased expression of the 50-kDa PLA2G6 was associated with a gestational age-related increase in endometrial calcium-independent PLA2 activity that was sensitive to inhibition by bromoenol lactone (P < 0.05). Longitudinal uterine strips isolated from gd10 or gd20 rat were suspended in muscle baths to evaluate uterine contractions following exposure to the ortho substituted congener PCB 50. Exposure to 50 and 100 microM PCB 50 significantly increased the frequency of gd20, but not gd10, uteri compared to solvent (dimethyl sulfoxide) controls (P < 0.05). Pharmacologic inhibition of PLA2G6, but not PLA2G2A, attenuated PCB-induced stimulation of gd20 uterine contractions (P < 0.05). These data suggest that PCB 50 stimulates uterine contractions by activating endometrial PLA2G6. Furthermore, gestation age-related sensitivity to PCB is associated with an increase in the expression of a previously unidentified 50-kDa PLA2G6 in rat uterus.

Secretory and cytosolic phospholipase A2 activities and expression are regulated by oxytocin and estradiol during labor

“…A decade passed by and Farrugia et al (1993) showed that type II PLA 2 is responsible for up to 80% of the total PLA 2 enzymatic activity present in placental tissues and that it represents the major component of PLA 2 activity in human fetal membranes at term (Aitken et al 1993). Recently, Brant et al (2006) showed a significant increase in rat uterine calciumindependent PLA 2 activity with the progression of labor. In the present work, we demonstrated a gestation-related increase of both the secretory and the cytosolic PLA 2 activities in the rat uterus.…”

“…Recently, Brant et al (2006) observed that sPLA 2 and cPLA 2 proteins are expressed in the rat uterus at mid (day 10) and late (day 20) pregnancy. Further evidence suggests that this enzyme could play a role in membrane remodeling but not in AA release (Murakami et al 1998).…”

Distinct phospholipase A2 enzymes regulate prostaglandin E2 and F2alpha production by bovine endometrial epithelial cells

“…Several splice variants of the enzyme are expressed yielding multiple molecular weight isoforms [25]. Recently, expression of a 50 kDa Group 6 enzyme in rat myometrium was associated with agonist-induced uterine contractions [26]. …”

Qing-Kai-Ling oral liquid alleviated pneumonia via regulation of intestinal flora and metabolites in rats

“…Further study revealed that the expression of genes (Pla2g2a, Pla2g5, Alox12e, and Cyp4a8) involved with arachidonic acid metabolism was increased in the Model group. Specifically, Pla2g2a and Pla2g5 genes, which are members of secretory phospholipase A2 family, can encode enzymes that liberate membrane phospholipids to produce free fatty acids such as AA (Brant et al, 2006). In addition, phospholipase A2 activity is increased under inflammation, causing elevated Alox12e gene expression, and the expression of pro-inflammatory cytokines is decreased after inhibition of Alox12e (Srikanth et al, 2018).…”