Source:http://linkedlifedata.com/resource/pubmed/id/11551528
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2001-9-11
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pubmed:abstractText |
We investigated the inhibitory effects of S-nitrosoglutathione (GSNO) on cell proliferation, DNA synthesis and several enzymatic activities using spontaneously immortalized human endothelial cells (ECV304). Proliferation of ECV304 was inhibited by GSNO in a dose-dependent manner (125-1000 microM). DNA synthesis was decreased 2 h after addition of GSNO to cells and was markedly repressed from 20 h after the addition. The activity of ribonucleotide reductase, a rate-limiting enzyme for DNA synthesis, was unchanged in GSNO-treated cells. GSNO inhibited less than 40% of mitochondrial respiration activity, and the membrane potential and cellular levels of ATP were not significantly decreased by GSNO. GSNO had no inhibitory effect on activities of glutathione peroxidase, glutathione S-transferase and glutathione reductase. However, glyoxalase I (Glo I) activity was decreased to 20% of the control level within 60 min, and was consistently repressed during exposure to GSNO for 20 h. A membrane-permeable Glo I inhibitor, S-bromobenzylglutathione diethylester, inhibited proliferation of ECV304 cells, while methylglyoxal (MG), a toxic metabolite generated during glycolysis and a substrate for Glo I, failed to inhibit the cell growth even at 100 microM. Glo I in several mammalian cell lines was inactivated by GSNO with a pI shift. Although we failed to detect accumulation of MG under conditions of Glo I inactivation, these results suggest that the inhibitory effects of GSNO on cell proliferation and DNA synthesis might be at least partly due to inactivation of Glo I.
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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/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Lactoylglutathione Lyase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Donors,
http://linkedlifedata.com/resource/pubmed/chemical/Pyruvaldehyde,
http://linkedlifedata.com/resource/pubmed/chemical/S-Nitrosoglutathione
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0009-2797
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
31
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pubmed:volume |
137
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
105-21
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:11551528-Animals,
pubmed-meshheading:11551528-Cell Division,
pubmed-meshheading:11551528-Cell Line,
pubmed-meshheading:11551528-DNA,
pubmed-meshheading:11551528-Glutathione,
pubmed-meshheading:11551528-Humans,
pubmed-meshheading:11551528-Lactoylglutathione Lyase,
pubmed-meshheading:11551528-Mitochondria,
pubmed-meshheading:11551528-Nitric Oxide Donors,
pubmed-meshheading:11551528-Pyruvaldehyde,
pubmed-meshheading:11551528-S-Nitrosoglutathione
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pubmed:year |
2001
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pubmed:articleTitle |
Inhibitory effects of S-nitrosoglutathione on cell proliferation and DNA synthesis: possible role of glyoxalase I inactivation.
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pubmed:affiliation |
School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Tokyo, 108-8641, Minato-ku, Japan.
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pubmed:publicationType |
Journal Article
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