title: PKC delta in preeclamptic placentas promotes Bax dissociation from 14-3-3 zeta through 14-3-3 zeta phosphorylation.
abstract: OBJECTIVE
  We 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.
  
  
  METHODS
  Placental 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.
  
  
  RESULTS
  M30-positive cells were widespread in the preeclamptic placentas. The levels of cleaved caspase-3, Bax, 14-3-3 zeta, phospho-(Ser)-14-3-3, and PKC delta were significantly higher in the preeclamptic placentas than in normal placentas. Preeclampsia was also associated with weaker interactions between 14-3-3 zeta and Bax and stronger interactions between 14-3-3 zeta and PKC delta.
  
  
  CONCLUSIONS
  Our results suggest that PKC delta in preeclamptic placentas promotes Bax dissociation from 14-3-3 zeta through the phosphorylation of 14-3-3 zeta. This finding may at least in part explain the apoptosis-inducing activity of PKC delta, revealing the important role of PKC delta in the development of apoptosis-related diseases such as preeclampsia.
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, Gyeongsang National University, 90 Chilam-dong, JinJu 660-702, Republic of Korea.
authors.forename: J K
authors.initials: JK
authors.lastname: Park
authors.forename: M Y
authors.initials: MY
authors.lastname: Kang
authors.forename: Y H
authors.initials: YH
authors.lastname: Kim
authors.forename: H C
authors.initials: HC
authors.lastname: Jo
authors.forename: J K
authors.initials: JK
authors.lastname: Shin
authors.forename: W J
authors.initials: WJ
authors.lastname: Choi
authors.forename: S A
authors.initials: SA
authors.lastname: Lee
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.forename: W S
authors.initials: WS
authors.lastname: Choi
authors.forename: W Y
authors.initials: WY
authors.lastname: Paik
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000328:Adult; D017209:Apoptosis / Q000502:physiology; D005260:Female; D006801:Humans; D008954:Models, Biological; D010766:Phosphorylation; D010920:Placenta / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D011225:Pre-Eclampsia / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011263:Pregnancy Trimester, Third / Q000378:metabolism; D011485:Protein Binding; D051745:Protein Kinase C-delta / Q000378:metabolism / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D051028:bcl-2-Associated X Protein; D051745:Protein Kinase C-delta