Source:http://linkedlifedata.com/resource/pubmed/id/10973919
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
2000-9-21
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pubmed:abstractText |
Reactive oxygen species (ROS) have been implicated as mediators of tumor necrosis factor-alpha (TNF) -induced apoptosis. In addition to leading to cell death, ROS can also promote cell growth and/or survival. We investigated these two roles of ROS in TNF-induced endothelial cell apoptosis. Human umbilical vein endothelial cells (HUVECs) stimulated with TNF produced an intracellular burst of ROS. Adenoviral-mediated gene transfer of a dominant negative form of the small GTPase Rac1 (Rac1N17) partially suppressed the TNF-induced oxidative burst without affecting TNF-induced mitochondrial ROS production. HUVECs were protected from TNF-induced apoptosis. Expression of Rac1N17 blocked TNF-induced activation of nuclear factor-kappa B (NF-kappaB), increased activity of caspase-3, and markedly augmented endothelial cell susceptibility to TNF-induced apoptosis. Direct inhibition of NF-kappaB through adenoviral expression of the super repressor form of inhibitor of kappaBalpha (I-kappaB S32/36A) also increased susceptibility of HUVECs to TNF-induced apoptosis. Rotenone, a mitochondrial electron transport chain inhibitor, suppressed TNF-induced mitochondrial ROS production, proteolytic cleavage of procaspase-3, and apoptosis. These findings show that Rac1 is an important regulator of TNF-induced ROS production in endothelial cells. Moreover, they suggest that Rac1-dependent ROS, directly or indirectly, lead to protection against TNF-induced death, whereas mitochondrial-derived ROS promote TNF-induced apoptosis.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/rac1 GTP-Binding Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0892-6638
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1705-14
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:10973919-Adenoviridae,
pubmed-meshheading:10973919-Apoptosis,
pubmed-meshheading:10973919-Caspase 3,
pubmed-meshheading:10973919-Caspases,
pubmed-meshheading:10973919-Cells, Cultured,
pubmed-meshheading:10973919-Endothelium, Vascular,
pubmed-meshheading:10973919-Enzyme Precursors,
pubmed-meshheading:10973919-Genetic Vectors,
pubmed-meshheading:10973919-Humans,
pubmed-meshheading:10973919-Mitochondria,
pubmed-meshheading:10973919-NF-kappa B,
pubmed-meshheading:10973919-Reactive Oxygen Species,
pubmed-meshheading:10973919-Respiratory Burst,
pubmed-meshheading:10973919-Tumor Necrosis Factor-alpha,
pubmed-meshheading:10973919-rac1 GTP-Binding Protein
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pubmed:year |
2000
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pubmed:articleTitle |
Rac1 inhibits TNF-alpha-induced endothelial cell apoptosis: dual regulation by reactive oxygen species.
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pubmed:affiliation |
Division of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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