Linked Life Data

10642312

Source:http://linkedlifedata.com/resource/pubmed/id/10642312

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1 Pt 2
pubmed:dateCreated
2000-2-7
pubmed:abstractText
Endothelin-1 (ET-1) may be involved in the induction of vascular hypertrophy in hypertension. ET-1 may also modulate vascular growth through the exertion of antiapoptotic effects. The omega3 fatty acids (omega3 FAs), which have antiproliferative effects in various cell types, may have a beneficial role in hypertension. We tested the hypothesis that ET-1 could act as a survival factor against omega3 FA-induced apoptosis and attempted to elucidate possible molecular mechanisms underlying the protective action of ET-1 on docosahexaenoic acid (DHA)-induced apoptosis. Mesenteric vascular smooth muscle cells were stimulated with DHA, a representative omega3 FA. Dose-response curves of DHA at different apoptotic stages were assessed with the use of flow cytometry: (1) very early: plasma membrane phosphatidylserine (PS) translocation; (2) early: change in mitochondrial transmembrane potential (DeltaPsim); and (3) late: cell cycle analysis. Expression of the proapoptotic protein bax and the antiapoptotic protein bcl-2 was determined with Western blot assay. The activity and the expression of caspase 3, which is a critical proteolytic enzyme involved in the death-signaling pathway, were evaluated with a fluorometric immunosorbent enzyme assay and Western blot analysis, respectively. Apoptosis, which was detected with PS translocation, DeltaPsim disruption, and cell cycle analysis, was increased dose dependently by DHA. DHA-induced apoptosis was attenuated through exposure to ET-1 for 1 hour before DHA in cell cycle analysis. The interference of ET-1 with DHA-induced apoptosis, as detected with cell cycle analysis, was not apparent at the membrane (PS translocation) or the mitochondrial (DeltaPsim) level. The increase in bax/bcl-2 ratio in DHA-stimulated cells was not affected by ET-1. However, DHA increased both caspase 3 activity and the active forms of caspase 3 (20 and 17 kDa), resulting in enhanced DNA fragmentation as shown through Hoechst staining and fluorescence microscopy, which were attenuated by ET-1 pretreatment. In conclusion, DHA, an omega3 FA, induced apoptosis in vascular smooth muscle cells in a dose-dependent manner. ET-1 exerted important protective effects through the attenuation of DHA-induced caspase 3 activation and subsequent DNA fragmentation in the late stages of apoptosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0194-911X
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
287-91
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10642312-Animals, pubmed-meshheading:10642312-Apoptosis, pubmed-meshheading:10642312-Biological Transport, pubmed-meshheading:10642312-Caspase 3, pubmed-meshheading:10642312-Caspases, pubmed-meshheading:10642312-Cell Cycle, pubmed-meshheading:10642312-Cell Membrane, pubmed-meshheading:10642312-Cells, Cultured, pubmed-meshheading:10642312-DNA Fragmentation, pubmed-meshheading:10642312-Docosahexaenoic Acids, pubmed-meshheading:10642312-Dose-Response Relationship, Drug, pubmed-meshheading:10642312-Endothelin-1, pubmed-meshheading:10642312-Membrane Potentials, pubmed-meshheading:10642312-Mesenteric Arteries, pubmed-meshheading:10642312-Muscle, Smooth, Vascular, pubmed-meshheading:10642312-Phosphatidylserines, pubmed-meshheading:10642312-Proto-Oncogene Proteins, pubmed-meshheading:10642312-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:10642312-Rats, pubmed-meshheading:10642312-Rats, Sprague-Dawley, pubmed-meshheading:10642312-bcl-2-Associated X Protein
pubmed:year
2000
pubmed:articleTitle
Endothelin-1 attenuates omega3 fatty acid-induced apoptosis by inhibition of caspase 3.
pubmed:affiliation
MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Montreal, Quebec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't