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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2010-8-20
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pubmed:abstractText |
This study investigated the role of NMDA receptor in hyperhomocyteinemia (hHcys)-induced NADPH oxidase (Nox) activation and glomerulosclerosis. Sprague-Dawley rats were fed a folate-free (FF) diet to produce hHcys, and a NMDA receptor antagonist, MK-801, was administrated. Rats fed the FF diet exhibited significantly increased plasma homocysteine levels, upregulated NMDA receptor expression, enhanced Nox activity and Nox-dependent O(2)(.-) production in the glomeruli, which were accompanied by remarkable glomerulosclerosis. MK-801 treatment significantly inhibited Nox-dependent O(2)(.-) production induced by hHcys and reduced glomerular damage index as compared with vehicle-treated hHcys rats. Correspondingly, glomerular deposition of extracellular matrix components in hHcys rats was ameliorated by the administration of MK-801. Additionally, hHcys induced an increase in tissue inhibitor of metalloproteinase-1 (TIMP-1) expression and a decrease in matrix metalloproteinase (MMP)-1 and MMP-9 activities, all of which were abolished by MK-801 treatment. In vitro studies showed that homocysteine increased Nox-dependent O(2)(.-) generation in rat mesangial cells, which was blocked by MK-801. Pretreatment with MK-801 also reversed homocysteine-induced decrease in MMP-1 activity and increase in TIMP-1 expression. These results support the view that the NMDA receptor may mediate Nox activation in the kidney during hHcys and thereby play a critical role in the development of hHcys-induced glomerulosclerosis.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1557-7716
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
975-86
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pubmed:dateRevised |
2011-10-3
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pubmed:meshHeading |
pubmed-meshheading:20406136-Animals,
pubmed-meshheading:20406136-Cell Line,
pubmed-meshheading:20406136-Dizocilpine Maleate,
pubmed-meshheading:20406136-Extracellular Matrix,
pubmed-meshheading:20406136-Folic Acid,
pubmed-meshheading:20406136-Gene Expression,
pubmed-meshheading:20406136-Hyperhomocysteinemia,
pubmed-meshheading:20406136-Kidney,
pubmed-meshheading:20406136-Kidney Diseases,
pubmed-meshheading:20406136-Kidney Glomerulus,
pubmed-meshheading:20406136-Matrix Metalloproteinase 1,
pubmed-meshheading:20406136-Matrix Metalloproteinase 9,
pubmed-meshheading:20406136-N-Methylaspartate,
pubmed-meshheading:20406136-NADPH Oxidase,
pubmed-meshheading:20406136-Rats,
pubmed-meshheading:20406136-Rats, Sprague-Dawley,
pubmed-meshheading:20406136-Receptors, N-Methyl-D-Aspartate,
pubmed-meshheading:20406136-Tissue Inhibitor of Metalloproteinase-1
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pubmed:year |
2010
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pubmed:articleTitle |
NMDA receptor-mediated activation of NADPH oxidase and glomerulosclerosis in hyperhomocysteinemic rats.
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pubmed:affiliation |
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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