Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-5-23
pubmed:abstractText
Clusterin is a stress-response protein that is involved in diverse biological processes, including cell proliferation, apoptosis, tissue differentiation, inflammation, and lipid transport. Its expression is upregulated in a broad spectrum of diverse pathological states. Clusterin was recently reported to be associated with diabetes, metabolic syndrome, and their sequelae. However, the regulation of clusterin expression by metabolic signals was not addressed. In this study we evaluated the effects of glucose on hepatic clusterin expression. Interestingly, high glucose concentrations significantly increased clusterin expression in primary hepatocytes and hepatoma cell lines, but the conventional promoter region of the clusterin gene did not respond to glucose stimulation. In contrast, the first intronic region was transcriptionally activated by high glucose concentrations. We then defined a glucose response element (GlRE) of the clusterin gene, showing that it consists of two E-box motifs separated by five nucleotides and resembles carbohydrate response element (ChoRE). Unexpectedly, however, these E-box motifs were not activated by ChoRE binding protein (ChREBP), but were activated by sterol regulatory element binding protein-1c (SREBP-1c). Furthermore, we found that glucose induced recruitment of SREBP-1c to the E-box of the clusterin gene intronic region. Taken together, these results suggest that clusterin expression is increased by glucose stimulation, and SREBP-1c plays a crucial role in the metabolic regulation of clusterin.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1090-2104
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
20
pubmed:volume
408
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
720-5
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
SREBP-1c regulates glucose-stimulated hepatic clusterin expression.
pubmed:affiliation
Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't