PKC δ in Preeclamptic Placentas Promotes Bax Dissociation from 14-3-3 ζ through 14-3-3 ζ Phosphorylation

ObjectiveWe investigated placental apoptosis and the expression of and interactions between 14-3-3 and Bcl-2 family proteins during preeclampsia. In addition, we explored the mechanism of Bax dissociation from 14-3-3, hypothesizing that PKC-mediated phosphorylation of 14-3-3 results in dissociation of Bax from 14-3-3 proteins, and leads to apoptosis.MethodsPlacental samples from 10 women with preeclampsia and 10 normotensive control patients were analyzed using M30-specific immunohistochemistry to assess placental apoptosis. Biochemical markers of cellular apoptosis, such as cleaved caspase-3, Bax, Bcl-2, 14-3-3, and PKC were followed by Western blotting. Interaction of 14-3-3 proteins with Bax and with PKC was assessed by immunoprecipitation.ResultsM30-positive cells were widespread in the preeclamptic placentas. The levels of cleaved caspase-3, Bax, 14-3-3 ζ, phospho-(Ser)-14-3-3, and PKC δ were significantly higher in the preeclamptic placentas than in normal placentas. Preeclampsia was also associated with weaker interactions between 14-3-3 ζ and Bax and stronger interactions between 14-3-3 ζ and PKC δ.ConclusionOur results suggest that PKC δ in preeclamptic placentas promotes Bax dissociation from 14-3-3 ζ through the phosphorylation of 14-3-3 ζ. This finding may at least in part explain the apoptosis-inducing activity of PKC δ, revealing the important role of PKC δ in the development of apoptosis-related diseases such as preeclampsia.