The effects of the phosphatase inhibitor, okadaic acid, on plasminogen activator expression in bovine oocyte-cumulus cell complexes

Abstract

Plasminogen activators (PAs) have been implicated in: ovulation, oocyte maturation, fertilization, implantation, and many other reproductive activities. Three pathways have been implicated in the activation of the PA regulatory system. These include the conventional PKC and cAMP-dependent signaling pathways, and also an independent pathway thought to be regulated by protein phosphatases. Previous research has suggested that PA activity in bovine oocyte-cumulus cell complexes (BOCC) is affected by okadaic acid (OA), a dose dependent phosphatase 1 (PP1) and 2A (PP2A) inhibitor (10 nM, 0.1 nM respectively) (Nagamine et al, 1991; Kim, 1995). The specific purpose of this research project was to determine the effects OA has on expression of the essential components of the PA system. We showed that OA affects the transcriptional levels of plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (tPA), and (3-actin. The uPA receptor (uPA-R) also expressed variability among its mRNA levels in a dose response to OA; however, the data were not significant. We also suggest that the PA system is involved in the BOCC's response to OA induced stress between the concentrations of 50-100 nM. In conclusion, PP1 and PP2A are essential to the expression of PAs in BOCC, and PP1 seems to be the predominant protein phosphatase driving PA expression.