Linked Life Data

19566842

Source:http://linkedlifedata.com/resource/pubmed/id/19566842

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-2-24
pubmed:abstractText
1. C/EBP homologueueueous protein (CHOP), an endoplasmic reticulum (ER) stress-inducible protein, has a critical role in regulation of the cell cycle and apoptosis by forming heterodimers with other C/EBP proteins. However, how CHOP function is regulated remains to be determined. The human homologue of Drosophila tribbles (TRIB3) is associated with CHOP and is upregulated by oxidized low-density lipoprotein (ox-LDL). The aim of the present study was to investigate the role of CHOP in ox-LDL-induced TRIB3 expression in macrophages. 2. Human monocyte-derived macrophages were treated with various concentrations of ox-LDL (0, 2.5, 5, 10, 25 and 50 microg/mL) or 2 microg/mL tunicamycin for 0, 4, 8, 16, 24 and 48 h or were transfected with CHOP or TRIB3 expression plasmid and TRIB3 targeting short interference RNA (siRNA). The expression of CHOP and activating transcription factor 4 (ATF4) mRNA in treated cells was detected by quantitative real-time polymerase chain reaction (PCR). 3. The expression of CHOP and ATF4 mRNA increased with increasing concentrations of ox-LDL and duration of time. The ox-LDL-induced expression of TRIB3 mRNA was upregulated later than the expression of CHOP and ATF4 mRNA. Overexpression of CHOP increased the mRNA expression of TRIB3, which was further increased in CHOP-overexpressing macrophages treated with ox-LDL. Overexpression of TRIB3 suppressed the expression of CHOP, whereas TRIB3 silencing increased CHOP expression following ox-LDL stimulation by a negative feedback mechanism. 4. In conclusion, the expression of ATF4 and CHOP is upregulated by ox-LDL in a dose- and time-dependent manner in naturally differentiated human macrophages. Oxidized LDL induces TRIB3 expression via an ATF4/CHOP-dependent ER stress pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Activating Transcription Factor 4, http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins, http://linkedlifedata.com/resource/pubmed/chemical/DDIT3 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, LDL, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering, http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/TRIB3 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor CHOP, http://linkedlifedata.com/resource/pubmed/chemical/Tunicamycin, http://linkedlifedata.com/resource/pubmed/chemical/oxidized low density lipoprotein
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1440-1681
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
51-5
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Tribble 3, a novel oxidized low-density lipoprotein-inducible gene, is induced via the activating transcription factor 4-C/EBP homologous protein pathway.
pubmed:affiliation
Department of Cardiology, Key Laboratory of Cardiovascular Remodelling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Ji'nan, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't