Source:http://linkedlifedata.com/resource/pubmed/id/12167592
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2002-8-8
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| pubmed:abstractText |
Lipid abnormalities and dysregulation of the plasminogen activator (PA)/plasmin system may be involved in the development of glomerulosclerosis. We investigated the effects of low-density lipoprotein (LDL) on PA inhibitor-1 (PAI-1), urokinase-type PA (uPA), and tissue-type PA (tPA) in relationship to protein kinase C (PKC) in cultured human mesangial cells (HMC). LDL (200 microg/ml) induced two peaks of PKC activation at hours 0.25 and 6, with translocation of PKC-alpha, -beta(1), and -delta from cytosol to the membrane. The second increase in PKC activity gradually decreased to the control value by hour 18. LDL downregulated 2.4-kb PAI-1, uPA, and tPA mRNA expression within 6 h of incubation with HMC. On the other hand, after 12-48 h, LDL-treated cells showed a significant increase in PAI-1, tPA, and uPA mRNA levels. LDL induced up to a twofold increase in PAI-1 antigen levels in the extracellular matrix of HMC after 24-48 h as well as increased PA inhibitory activity in the culture medium. Analysis of the adhesion plaques from cells incubated with LDL for 48 h by zymography showed increased intensity of lysis near molecular weights of approximately 55,000 and 100,000. LDL slightly increased tPA release at hours 24 and 48 but did not increase PA activity in culture medium. The stimulatory effects of LDL on PAI-1, tPA, and uPA gene regulation in HMC were blocked by the inhibition of PKC using GF-109203X 12 h after treatment with LDL or downregulation of PKC using phorbol myristate acetate. In summary, LDL regulates PAI-1, uPA, and tPA in biphasic patterns in HMC, and the upregulation of PAI-1, uPA, and tPA after long-term LDL exposure seems to be mediated by a delayed PKC activation associated with an increased PA inhibitory activity. These results suggest that LDL, after prolonged incubations with HMC, causes a PA/inhibitor imbalance favoring accumulation of matrix.
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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/Amiloride,
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Conditioned,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, LDL,
http://linkedlifedata.com/resource/pubmed/chemical/Maleimides,
http://linkedlifedata.com/resource/pubmed/chemical/Plasminogen Activator Inhibitor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Tissue Plasminogen Activator,
http://linkedlifedata.com/resource/pubmed/chemical/Urokinase-Type Plasminogen Activator,
http://linkedlifedata.com/resource/pubmed/chemical/Vitamin E,
http://linkedlifedata.com/resource/pubmed/chemical/bisindolylmaleimide I
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
1931-857X
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
283
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
F423-30
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| pubmed:dateRevised |
2011-4-28
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| pubmed:meshHeading |
pubmed-meshheading:12167592-Amiloride,
pubmed-meshheading:12167592-Antioxidants,
pubmed-meshheading:12167592-Cells, Cultured,
pubmed-meshheading:12167592-Culture Media, Conditioned,
pubmed-meshheading:12167592-Enzyme Activation,
pubmed-meshheading:12167592-Enzyme Inhibitors,
pubmed-meshheading:12167592-Extracellular Matrix,
pubmed-meshheading:12167592-Fibrinolysis,
pubmed-meshheading:12167592-Gene Expression Regulation,
pubmed-meshheading:12167592-Glomerular Mesangium,
pubmed-meshheading:12167592-Humans,
pubmed-meshheading:12167592-Indoles,
pubmed-meshheading:12167592-Lipoproteins, LDL,
pubmed-meshheading:12167592-Maleimides,
pubmed-meshheading:12167592-Plasminogen Activator Inhibitor 1,
pubmed-meshheading:12167592-Protein Kinase C,
pubmed-meshheading:12167592-RNA, Messenger,
pubmed-meshheading:12167592-Tissue Plasminogen Activator,
pubmed-meshheading:12167592-Urokinase-Type Plasminogen Activator,
pubmed-meshheading:12167592-Vitamin E
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| pubmed:year |
2002
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| pubmed:articleTitle |
Biphasic regulation of plasminogen activator/inhibitor by LDL in mesangial cells.
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| pubmed:affiliation |
Department of Pathology, Seoul National University College of Medicine, Korea.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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