| Pathologically elevated cyclic hydrostatic pressure induces CD95-mediated apoptotic cell death in vascular endothelial cells. | |
MedLine Citation:
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PMID: 15772124 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We describe cyclic hydrostatic pressure of 200/100 mmHg with a frequency of 85/min as a hemodynamically relevant pathological condition enforcing apoptosis in endothelial cells (EC) after 24 h of treatment. This went along with an increase of CD95 and CD95L surface expression, shedding of CD95L into the supernatant, cleavage of caspase-3 and caspase-8, and elevated JNK-2, c-Jun, and CD95L mRNA expression. Furthermore, increased DNA-binding activity of the AP-1 transcription factor family members FRA-1 and c-Jun was observed. This activation was reduced by inhibition of JNK, which subsequently prevented elevated CD95L mRNA expression. Caspase inhibitors and a CD95L-neutralizing antibody also reduced EC apoptosis. Most of the pressure-induced events were most prominent at 24 and 48 h. However, after 48 h, the CD95/CD95L expression pattern switched back to CD95-/CD95L+ and the specific death rate decreased. Cyclic pathological hydrostatic pressure is a novel type of stress to EC that renders them susceptible to CD95/CD95L-mediated autoapoptosis and/or paracrine apoptosis accompanied by upregulation of intracellular molecules known to trigger both apoptosis and survival. |
Authors:
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Cornelia Hasel; Susanne Dürr; Anke Bauer; Rene Heydrich; Silke Brüderlein; Tabe Tambi; Umesh Bhanot; Peter Möller |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2005-03-16 |
Journal Detail:
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Title: American journal of physiology. Cell physiology Volume: 289 ISSN: 0363-6143 ISO Abbreviation: Am. J. Physiol., Cell Physiol. Publication Date: 2005 Aug |
Date Detail:
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Created Date: 2005-07-08 Completed Date: 2005-08-11 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 100901225 Medline TA: Am J Physiol Cell Physiol Country: United States |
Other Details:
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Languages: eng Pagination: C312-22 Citation Subset: IM |
Affiliation:
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Institute of Pathology, University of Ulm, Ulm, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, CD95
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biosynthesis* Aorta / cytology Apoptosis / drug effects, physiology* Caspases / drug effects, metabolism Cells, Cultured Electrophoretic Mobility Shift Assay Endothelial Cells / metabolism, pathology* Enzyme Activation / physiology Enzyme Inhibitors / pharmacology Enzyme-Linked Immunosorbent Assay Fas Ligand Protein Flow Cytometry Humans Hydrostatic Pressure Immunoblotting Membrane Glycoproteins / biosynthesis Reverse Transcriptase Polymerase Chain Reaction Transcription Factors Umbilical Veins / cytology |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD95; 0/Enzyme Inhibitors; 0/FASLG protein, human; 0/Fas Ligand Protein; 0/Membrane Glycoproteins; 0/Transcription Factors; EC 3.4.22.-/Caspases |
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