Hyperglycemia induced activation of type-1 protein phosphatase activator (kinase FA) in perfused human placenta

We report the identification of type-1 protein phosphatase activating factor (kinase FA), a unique biologic mediator for both insulin and epidermal growth factors in the human placenta. The activity of kinase F, was found to be extremely labile in the unperfused placenta. Fresh term placentas lost more than 50% of the total kinase FA activity within 6 hours when exposed to air of incubated in medium but not perfused. In contrast, the activity of kinase FA was stable when the human term placenta was dually perfused. This indicates that placental dual perfusion is a useful method for studying protein phosphorylation-dephosphorylation involved in signal transduction. When fresh placentas were perfused with media containing glucose at 141 +/- 10, 242 +/- 12 and 436 +/- 20 mg/dL, kinase FA activity was stimulated several-fold in a glucose concentration-dependent manner when compared with control levels at delivery. The results suggest that hyperglycemia-mediated activation may represent a previously unknown control mechanisms for the regulation of protein kinase FA. The results also suggest that human placental perfusion is a good in vitro system for studying signal transduction mechanisms involved in hormonal actions and metabolic regulation.