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Article: Homocysteine induces monocyte chemoattractant protein-1 expression in hepatocytes mediated via activator protein-1 activation

TitleHomocysteine induces monocyte chemoattractant protein-1 expression in hepatocytes mediated via activator protein-1 activation
Authors
Issue Date2008
Citation
Journal of Biological Chemistry, 2008, v. 283 n. 3, p. 1282-1292 How to Cite?
AbstractHyperhomocysteinemia is characterized by abnormally high concentrations of homocysteine (Hcy) in the plasma. It is a metabolic disorder associated with dysfunction of several organs such as atherosclerosis, altered lipid metabolism, and liver injury. In this study we investigated the effect of Hcy on transcriptional regulation of monocyte chemoattractant protein-1 (MCP-1), a potent chemokine, expression in hepatocytes. Hyperhomocysteinemia was induced in rats by a high-methionine diet for 4 weeks. MCP-1 mRNA and protein levels were significantly elevated in the liver tissue homogenate and in hepatocytes of hyperhomocysteinemic rats. The role of transcription factors in MCP-1 expression was examined by electrophoretic mobility shift assay. Activation of activator protein (AP)-1 but not nuclear factor κB was detected in the liver tissue of those rats. Incubation of rat hepatocytes with Hcy (50-200 μM) caused a significant increase in AP-1 activation followed by an increase in intracellular MCP-1 mRNA expression and an elevation of MCP-1 protein secreted into the culture medium. Hcy markedly increased the DNA binding activity of human recombinant AP-1 (c-Fos and c-Jun proteins). The presence of a sulfhydryl group in Hcy was essential for Hcy-induced AP-1 activation. When hepatocytes were transfected with decoy AP-1 oligodeoxynucleotide to inhibit AP-1 activation, Hcy-induced MCP-1 mRNA expression was abolished. Further analysis revealed that increased hepatic MCP-1 expression was positively correlated with the serum MCP-1 level. These results suggest that Hcy-induced MCP-1 expression in the liver is mediated via AP-1 activation, which may contribute to chronic inflammation associated with hyperhomocysteinemia. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/194206
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWoo, CWH-
dc.contributor.authorSiow, YL-
dc.contributor.authorO, K-
dc.date.accessioned2014-01-30T03:32:18Z-
dc.date.available2014-01-30T03:32:18Z-
dc.date.issued2008-
dc.identifier.citationJournal of Biological Chemistry, 2008, v. 283 n. 3, p. 1282-1292-
dc.identifier.issn0021-9258-
dc.identifier.urihttp://hdl.handle.net/10722/194206-
dc.description.abstractHyperhomocysteinemia is characterized by abnormally high concentrations of homocysteine (Hcy) in the plasma. It is a metabolic disorder associated with dysfunction of several organs such as atherosclerosis, altered lipid metabolism, and liver injury. In this study we investigated the effect of Hcy on transcriptional regulation of monocyte chemoattractant protein-1 (MCP-1), a potent chemokine, expression in hepatocytes. Hyperhomocysteinemia was induced in rats by a high-methionine diet for 4 weeks. MCP-1 mRNA and protein levels were significantly elevated in the liver tissue homogenate and in hepatocytes of hyperhomocysteinemic rats. The role of transcription factors in MCP-1 expression was examined by electrophoretic mobility shift assay. Activation of activator protein (AP)-1 but not nuclear factor κB was detected in the liver tissue of those rats. Incubation of rat hepatocytes with Hcy (50-200 μM) caused a significant increase in AP-1 activation followed by an increase in intracellular MCP-1 mRNA expression and an elevation of MCP-1 protein secreted into the culture medium. Hcy markedly increased the DNA binding activity of human recombinant AP-1 (c-Fos and c-Jun proteins). The presence of a sulfhydryl group in Hcy was essential for Hcy-induced AP-1 activation. When hepatocytes were transfected with decoy AP-1 oligodeoxynucleotide to inhibit AP-1 activation, Hcy-induced MCP-1 mRNA expression was abolished. Further analysis revealed that increased hepatic MCP-1 expression was positively correlated with the serum MCP-1 level. These results suggest that Hcy-induced MCP-1 expression in the liver is mediated via AP-1 activation, which may contribute to chronic inflammation associated with hyperhomocysteinemia. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.-
dc.languageeng-
dc.relation.ispartofJournal of Biological Chemistry-
dc.titleHomocysteine induces monocyte chemoattractant protein-1 expression in hepatocytes mediated via activator protein-1 activation-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1074/jbc.M707886200-
dc.identifier.pmid18024959-
dc.identifier.scopuseid_2-s2.0-38549177421-
dc.identifier.volume283-
dc.identifier.issue3-
dc.identifier.spage1282-
dc.identifier.epage1292-
dc.identifier.isiWOS:000252282700011-

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