| Modulation of trophoblast cell death by oxygen and EGF. | |
| | |
MedLine Citation:
|
PMID: 12606820 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND: Preeclampsia, a maternal hypertensive disease, is characterized by shallow invasion of the maternal spiral arterioles resulting in hypoxia/reperfusion type insult; however, the molecular mechanism is unknown. The aim of this study was to determine the mechanism of altered oxygen tension or inhibition of phosphatidyl-inositol-3-kinase (PI3K) on trophoblast survival and to investigate the effect of epidermal growth factor (EGF) on maintaining cellular integrity. MATERIALS AND METHOD: We have used flow cytometry, immunoblotting, and fluoroimmunocytochemistry to study apoptosis in a characterized, spontaneously transformed first trimester extravillous-like trophoblast cell line that exhibits many characteristics of in vivo trophoblast. RESULTS: Time-dependent exposure of first trimester extravillous-like trophoblast to all oxygen tensions tested promoted dissipation of the mitochondrial membrane potential (psi(m)) and resulted in a significant increase in celldeath by 48 hr as determined by dual staining flow cytometry. Western blot analysis revealed expression ofcleaved caspase-3 and caspase-9 increased with time with hypoxia and hyperoxia promoting the greatest elevation indicating that longer duration of exposure to a change inoxygen tension causes increased apoptosis via a mitochondrial-mediated pathway. Disruption of the anti-apoptotic PI3K pathway by LY294002 (40 microM), its specific inhibitor, caused further significant dissipation of the psi(m) (p< 0.01) and cleavage of caspase-3. EGF was able to maintain the psi(m) and to prevent cleavage of caspase-3 even in the presence of LY294002, indicating that its survival effects were independent of the PI3K pathway. CONCLUSIONS: These results suggest that inhibition of the PI3K/Akt pathway can sensitize first-trimester trophoblast-like cells into oxygen-induced cell death and that EGF exerts its anti-apoptotic effect independently of PI3K/Akt. |
| | |
Authors:
|
Jonathan Perkins; Justin St John; Asif Ahmed |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Molecular medicine (Cambridge, Mass.) Volume: 8 ISSN: 1076-1551 ISO Abbreviation: Mol. Med. Publication Date: 2002 Dec |
Date Detail:
|
Created Date: 2003-02-27 Completed Date: 2003-08-01 Revised Date: 2008-11-20 |
Medline Journal Info:
|
Nlm Unique ID: 9501023 Medline TA: Mol Med Country: United States |
Other Details:
|
Languages: eng Pagination: 847-56 Citation Subset: IM |
Affiliation:
|
Department of Reproductive and Vascular Biology, The Medical School, University of Birmingham, Birmingham, UK. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
1-Phosphatidylinositol 3-Kinase
/
antagonists & inhibitors Caspases / metabolism Cell Death / drug effects, physiology* Cell Line Culture Media Epidermal Growth Factor / metabolism*, pharmacology Flow Cytometry Humans Oxygen / metabolism*, pharmacology Trophoblasts / metabolism* |
| Chemical | |
Reg. No./Substance:
|
0/Culture Media; 62229-50-9/Epidermal Growth Factor; 7782-44-7/Oxygen; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Peripheral benzodiazepine binding sites in platelets of patients affected by mitochondrial diseases ...
Next Document: Farnesyl protein transferase inhibition interferes with activation of MAP kinase family members in h...