PKC delta in preeclamptic placentas promotes Bax dissociation from 14-3-3 zeta through 14-3-3 zeta phosphorylation.
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.
Park
J K
JK
Department of Obstetrics and Gynecology, College of Medicine, Gyeongsang National University, 90 Chilam-dong, JinJu 660-702, Republic of Korea.
Kang
M Y
MY
Kim
Y H
YH
Jo
H C
HC
Shin
J K
JK
Choi
W J
WJ
Lee
S A
SA
Lee
J H
JH
Choi
W S
WS
Paik
W Y
WY
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*
D048948:14-3-3 Proteins; D051028:bcl-2-Associated X Protein; D051745:Protein Kinase C-delta