TRIB3, a novel ox-LDL-inducible gene, is induced via the ATF4/CHOP pathway. Clinical and experimental pharmacology & physiology [Clin Exp Pharmacol Physiol] Journal article | | Title | TRIB3, a novel ox-LDL-inducible gene, is induced via the ATF4/CHOP pathway. | | Author(s) | Shang YY, Zhong M, Zhang LP, Guo ZX, Wang ZH, Zhang Y, Deng JT, Zhang W | | Institution | Key Laboratory of Cardiovascular Remodeling and Function Research, Department of Cardiology, Qilu Hospital of Shandong University, Ji'nan, P.R. China. | | Source | Clin Exp Pharmacol Physiol 2009 Jun 29. | | Abstract | 1. C/EBP homologous protein (CHOP), an endoplasmic reticulum (ER) stress-inducible protein, plays a critical role in the regulation of the cell cycle and apoptosis by forming heterodimers with other C/EBP proteins; however, the regulation of its function remains to be elucidated. The human homolog of Drosophila tribbles (TRIB3) is associated with CHOP and is upregulated by oxidized low-density lipoprotein (ox-LDL). The present study investigated 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 or 2 mug/ml tunicamycin for various times, or were transfected with CHOP or TRIB3 expression plasmid and TRIB3 targeting small-interfering RNA (siRNA). The expression of CHOP and ATF4 mRNA of the treated cells were detected by Quantitative real-time PCR. 3. The expression of CHOP and ATF4 mRNA increased with increasing ox-LDL concentrations and treatment time and the expression of TRIB3 mRNA induced by ox-LDL was upregulated later than that 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 under ox-LDL stimulation by a negative feedback mechanism. 4. The expressions of ATF4 and CHOP are upregulated by ox-LDL in a dose- and time-dependent manner in naturally differentiated human macrophages. Ox-LDL induces TRIB3 expression via an ATF4/CHOP-dependent ER stress pathway. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19566842 |
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