ArticleThe American journal of pathology2007
Hypoxic switch in mitochondrial myeloid cell leukemia factor-1/Mtd apoptotic rheostat contributes to human trophoblast cell death in preeclampsia.
Article in The American journal of pathology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 55 citations in OpenAlex.
- Understanding the intersection between placental development and cancer: Lessons from the tumor suppressor BAP1.Communications biology · 2024Review
- Diagnosis, Prevention, and Management of Fetal Growth Restriction (FGR).Journal of personalized medicine · 2024Review
- Ancestry dependent balancing selection of placental dysferlin at high-altitude.Frontiers in cell and developmental biology · 2023Article
- CLDN1 regulates trophoblast apoptosis and proliferation in preeclampsia.Reproduction (Cambridge, England) · 2021Article
- The Multifaceted Roles of the BCL-2 Family Member BOK.Frontiers in cell and developmental biology · 2020Review
- lncRNA TUG1 modulates proliferation, apoptosis, invasion, and angiogenesis via targeting miR-29b in trophoblast cells.Human genomics · 2019Article
- Upregulation of syncytin-1 promotes invasion and metastasis by activating epithelial-mesenchymal transition-related pathway in endometrial carcinoma.OncoTargets and therapy · 2019Article
- Ceramide-induced BOK promotes mitochondrial fission in preeclampsia.Cell death & disease · 2018Article
- Identification of key microRNAs and genes in preeclampsia by bioinformatics analysis.PloS one · 2017Article
- BCL-2 family member BOK promotes apoptosis in response to endoplasmic reticulum stress.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Disruption of sphingolipid metabolism augments ceramide-induced autophagy in preeclampsia.Autophagy · 2015Article
- Decreased expression and activation of Stat3 in severe preeclampsia.Journal of molecular histology · 2015Article
- Oxidative Stress in Placenta: Health and Diseases.BioMed research international · 2015Review
- Hypoxic stress induces, but cannot sustain trophoblast stem cell differentiation to labyrinthine placenta due to mitochondrial insufficiency.Stem cell research · 2014Article
- Preeclampsia is associated with alterations in the p53-pathway in villous trophoblast.PloS one · 2014Article
- Placental autophagy regulation by the BOK-MCL1 rheostat.Autophagy · 2013Article
- High temperature requirement A1 in placental tissues and serum from pre-eclamptic pregnancies with or without fetal growth restriction.Archives of medical science : AMS · 2013Article
- The double life of MULE in preeclamptic and IUGR placentae.Cell death & disease · 2012Article
- Non-viral systemic delivery of siRNA or antisense oligonucleotides targeted to Jun N-terminal kinase 1 prevents cellular hypoxic damage.Drug delivery and translational research · 2011Article
- Hypoxia downregulates p53 but induces apoptosis and enhances expression of BAD in cultures of human syncytiotrophoblasts.American journal of physiology. Cell physiology · 2010Article
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Preeclampsia, a disorder of pregnancy, is characterized by increased trophoblast cell death and altered trophoblast-mediated remodeling of myometrial spiral arteries resulting in reduced uteroplacental perfusion. Mitochondria-associated Bcl-2 family members are important regulators of programed cell death. The mechanism whereby hypoxia alters the mitochondrial apoptotic rheostat is essential to our understanding of placental disease. Herein, myeloid cell leukemia factor-1 (Mcl-1) isoform expression was examined in physiological/pathological models of placental hypoxia. Preeclamptic placentae were characterized by caspase-dependent cleavage of death-suppressing Mcl-1L and switch toward cell death-inducing Mcl-1S. In vitro, Mcl-1L cleavage was induced by hypoxia-reoxygenation in villous explants, whereas Mcl-1L overexpression under hypoxia-reoxygenation rescued trophoblast cells from undergoing apoptosis. Cleavage was mediated by caspase-3/-7 because pharmacological caspase inhibition prevented this process. Altitude-induced chronic hypoxia was characterized by expression of Mcl-1L; resulting in a reduction of apoptotic markers (cleaved caspase-3/-8 and p85 poly-ADP-ribose polymerase). Moreover, in both physiological (explants and high altitude) and pathological (preeclampsia) placental hypoxia, decreased trophoblast syncytin expression was observed. Hence, although both pathological and physiological placental hypoxia are associated with slowed trophoblast differentiation, trophoblast apoptosis is only up-regulated in preeclampsia, because of a hypoxia-reoxygenation-induced switch in generation of proapoptotic Mcl-1 isoforms.
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