Linked Life Data

19013297

Source:http://linkedlifedata.com/resource/pubmed/id/19013297

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2008-11-17
pubmed:abstractText
Human serum paraoxonase 1 (PON1) is associated with high-density lipoprotein and inhibits oxidative modification of low-density lipoprotein in vitro. Therefore, PON1 is expected to protect against atherosclerosis in vivo. We and other investigators have shown that PON1 enzymatic activity is decreased in diabetic patients; however, an alteration in hepatic PON1 synthesis under hyperglycemic conditions remains unclear. We previously demonstrated that Sp1 is a positive regulator of PON1 transcription and that an interaction between Sp1 and protein kinase C (PKC) is a crucial mechanism for the effect of Sp1 on PON1 transcription in cultured HepG2 cells. Because several PKC isoforms are activated under hyperglycemic conditions, we examined the effect of d-glucose, which can activate the diacylglycerol-PKC pathway, on the transcription and expression of PON1. For a reporter gene assay, Huh7 human hepatocyte cell line incorporated with PON1 (-1232/-6)-luciferase expression vector was established using a cationic lipid method. d-Glucose dose dependently enhanced PON1 promoter activity. d-Glucose also enhanced both messenger RNA and protein expression of PON1. Increased PON1 expression was also detected in primary human hepatocytes treated with high d-glucose concentrations. Bisindolylmaleimide, a PKC inhibitor, significantly inhibited d-glucose-induced transactivation of PON1; and mithramycin, an inhibitor of Sp1, completely abrogated the transactivation. Our data suggest that high glucose concentrations transactivate the PON1 gene through Sp1 activation by PKC in cultured hepatocytes. Up-regulated hepatic PON1 expression under high glucose conditions may be a compensatory mechanism in diabetes in which antioxidant capacity, including PON1 enzymatic activity, is attenuated.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1532-8600
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
57
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1725-32
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
High glucose induces transactivation of the human paraoxonase 1 gene in hepatocytes.
pubmed:affiliation
Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan.
pubmed:publicationType
Journal Article