PMID- 15775999
OWN - NLM
STAT- MEDLINE
DCOM- 20050901
LR  - 20070607
IS  - 1350-9047 (Print)
IS  - 1350-9047 (Linking)
VI  - 12
IP  - 5
DP  - 2005 May
TI  - A novel Mtd splice isoform is responsible for trophoblast cell death in 
      pre-eclampsia.
PG  - 441-52
AB  - Pre-eclampsia is a serious disorder of human pregnancy, characterized by 
      decreased utero-placental perfusion and increased trophoblast cell death. 
      Presently, the mechanisms regulating trophoblast cell death in pre-eclampsia are 
      not fully elucidated. Herein, we have identified a novel Mtd/Bok splice isoform 
      (Mtd-P) resulting from exon-II skipping. Mtd-P expression was unique to 
      early-onset severe pre-eclamptic placentae as assessed by quantitative 
      real-time-PCR and immunoblotting. Mtd-P overexpression in cell lines (BeWo: 
      cytotrophoblast-derived; and CHO: ovary-derived) resulted in increased apoptotic 
      cell death as assessed by caspase-3 cleavage, internucleosomal DNA laddering and 
      mitochondrial depolarization. Moreover, Mtd-P expression increased under 
      conditions of low oxygenation/oxidative stress in human villous explants. 
      Antisense knockdown of Mtd under conditions of oxidative stress resulted in 
      decreased caspase-3 cleavage. We conclude that under conditions of reduced 
      oxygenation/oxidative stress, Mtd-P causes trophoblast cell death in 
      pre-eclampsia and hence may contribute to the molecular events leading to the 
      clinical manifestations of this disease.
FAU - Soleymanlou, N
AU  - Soleymanlou N
AD  - Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
FAU - Wu, Y
AU  - Wu Y
FAU - Wang, J X
AU  - Wang JX
FAU - Todros, T
AU  - Todros T
FAU - Ietta, F
AU  - Ietta F
FAU - Jurisicova, A
AU  - Jurisicova A
FAU - Post, M
AU  - Post M
FAU - Caniggia, I
AU  - Caniggia I
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Cell Death Differ
JT  - Cell death and differentiation
JID - 9437445
RN  - 0 (BOK protein, human)
RN  - 0 (Protein Isoforms)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
SB  - IM
MH  - *Alternative Splicing
MH  - Amino Acid Sequence
MH  - *Cell Death
MH  - Female
MH  - Humans
MH  - Membrane Potentials
MH  - Mitochondria/physiology
MH  - Models, Biological
MH  - Molecular Sequence Data
MH  - Oxidative Stress
MH  - Placenta/cytology
MH  - Pre-Eclampsia/metabolism/*pathology
MH  - Pregnancy
MH  - Pregnancy Trimester, First
MH  - Protein Isoforms/genetics/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2
MH  - Trophoblasts/*pathology
EDAT- 2005/03/19 09:00
MHDA- 2005/09/02 09:00
CRDT- 2005/03/19 09:00
PHST- 2005/03/19 09:00 [pubmed]
PHST- 2005/09/02 09:00 [medline]
PHST- 2005/03/19 09:00 [entrez]
AID - 4401593 [pii]
AID - 10.1038/sj.cdd.4401593 [doi]
PST - ppublish
SO  - Cell Death Differ. 2005 May;12(5):441-52. doi: 10.1038/sj.cdd.4401593.