Faculty Research Mentor: Scott Barnett, Ph.D.2
1Nevada State College, Department of Biochemistry and Molecular Biology
2University of Nevada, Reno, Department of Cell and Molecular Pharmacology and Physiology
Approximately 15 million preterm births occur annually worldwide. These account for 1 in 10 pregnancies and constitute $51,000 in additional medical fees compared to a normal term birth. Currently, there are no FDA-approved drugs that reliably halt spontaneous preterm labor (sPTL). The myometrium, which is the muscle of the uterus, relaxes when exposed to nitric oxide (NO), but through a non-canonical process called S-nitrosation. Cx43 is a gap junction channel (GJC) in the myometrium critical to contraction and relaxation. Here we examined if Cx43 is dysregulated in in women who experience preterm labor (PTL) and if S-nitrosation of Cx43 affects its function. In the myometrium, Cx43 expression increased significantly during pregnancy (preterm non-labor P=0.0033, n=6; term labor P<0.0001, n=14; term non-labor P<0.0001, n=14), with the notable exception of PTL myometrium (n=6, P=0.8411), for which there was no appreciable increase in expression of Cx43. The expression of Cx43 in the myometrium is only one of several important metrics when establishing its role in contractile dynamics. It is well-known that Cx43’s phosphorylation state, particularly at S368, is critical to facilitating transition from the GJC (contraction) to the phosphorylated hemichannel (quiescent) state. We determined that the ratio of pS368:S368 was 2.6-fold higher (P=0.0281) in myometrium treated with NO as compared to tissue treated with oxytocin, suggesting a role of S-nitrosation in GJC disassembly. Because there are no effective therapies to treat PTL, these novel finding may be used to identify new therapies that target Cx43 dysregulation and phosphorylation during pregnancy.