Platelet-Derived Growth Factor Enhances Sp1 Binding to the LDL Receptor Gene

Basheeruddin, Khaja; Li, Xiaoli; Rechtoris, Carol; Mazzone, Theodore

doi:10.1161/01.atv.15.8.1248

Cited by 10 publications

(8 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…THP-1 cells were selected because they represent an established monocytic cell model (27) in which a relatively low endogenous C/EBPβ level can be detected according to their premonocytic developmental stage (see also Fig. 1 A ).…”

Section: Resultsmentioning

confidence: 99%

CCAAT/Enhancer-binding Protein β Inhibits Proliferation in Monocytic Cells by Affecting the Retinoblastoma Protein/E2F/Cyclin E Pathway but Is Not Directly Required for Macrophage Morphology

Gutsch

Kandemir

Pietsch

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Monocytic differentiation is orchestrated by complex networks that are not fully understood. This study further elucidates the involvement of transcription factor CCAAT/enhancer-binding protein β (C/EBPβ). Initially, we demonstrated a marked increase in nuclear C/EBPβ-liver-enriched activating protein* (LAP*)/liver-enriched activating protein (LAP) levels and LAP/liver-enriched inhibiting protein (LIP) ratios in phorbol 12-myristate 13-acetate (PMA)-treated differentiating THP-1 premonocytic cells accompanied by reduced proliferation. To directly study C/EBPβ effects on monocytic cells, we generated novel THP-1-derived (low endogenous C/EBPβ) cell lines stably overexpressing C/EBPβ isoforms. Most importantly, cells predominantly overexpressing LAP* (C/EBPβ-long), but not those overexpressing LIP (C/EBPβ-short), exhibited a reduced proliferation, with no effect on morphology. PMA-induced inhibition of proliferation was attenuated in C/EBPβ-short cells. In C/EBPβWT macrophage-like cells (high endogenous C/EBPβ), we measured a reduced proliferation/cycling index compared with C/EBPβKO. The typical macrophage morphology was only observed in C/EBPβWT, whereas C/EBPβKO stayed round. C/EBPα did not compensate for C/EBPβ effects on proliferation/morphology. Serum reduction, an independent approach known to inhibit proliferation, induced macrophage morphology in C/EBPβKO macrophage-like cells but not THP-1. In PMA-treated THP-1 and C/EBPβ-long cells, a reduced phosphorylation of cell cycle repressor retinoblastoma was found. In addition, C/EBPβ-long cells showed reduced c-Myc expression accompanied by increased CDK inhibitor p27 and reduced cyclin D1 levels. Finally, C/EBPβ-long and C/EBPβWT cells exhibited low E2F1 and cyclin E levels, and C/EBPβ overexpression was found to inhibit cyclin E1 promoter-dependent transcription. Our results suggest that C/EBPβ reduces monocytic proliferation by affecting the retinoblastoma/E2F/cyclin E pathway and that it may contribute to, but is not directly required for, macrophage morphology. Inhibition of proliferation by C/EBPβ may be important for coordinated monocytic differentiation.

show abstract

Section: Resultsmentioning

confidence: 99%

CCAAT/Enhancer-binding Protein β Inhibits Proliferation in Monocytic Cells by Affecting the Retinoblastoma Protein/E2F/Cyclin E Pathway but Is Not Directly Required for Macrophage Morphology

Gutsch

Kandemir

Pietsch

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…For the balance of the experiments, therefore, representative results using different incubation conditions are shown. We have previously reported that the expression of macrophage apoE can be regulated at transcriptional and post-transcriptional loci (25,28,29). For the current report, we elected to focus on a series of experiments to determine whether fatty acids regulated macrophage apoE expression at a post-transcriptional locus.…”

Section: Resultsmentioning

confidence: 99%

Oleic Acid Modulates the Post-translational Glycosylation of Macrophage ApoE to Increase Its Secretion

Huang

Mazzone

2004

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

There has been increasing interest in a potential role for fatty acids in adversely affecting organismal substrate utilization and contributing to the cardiovascular complications in insulin resistance. Fatty acids have already been implicated in regulating the expression of a number of genes in resident cells of the vessel wall. In the current studies, we evaluated a potential role for fatty acids in the regulation of macrophage apoE expression. Incubation in oleic acid increased the synthesis and secretion of apoE by human monocyte-derived macrophages. Part of this stimulation was mediated at a posttranslational locus. Oleic acid increased the secretion of apoE from macrophages that constitutively expressed a human apoE3 cDNA. Incubation in palmitic acid decreased apoE secretion from these cells. The effect of oleic acid on apoE secretion could not be accounted for by the known effect of fatty acid on cellular sterol, because incubation in oleic acid did not suppress the degradation of nascent apoE. Incubation in oleic acid for at least 6 h was required to observe an effect on apoE secretion. Oleic acid altered the glycosylation pattern of cellular and secreted apoE, with a loss of the most heavily sialylated isoform. Oleic acid had no effect on the glycosylation of interleukin 6 secreted from macrophages. Elimination of apoE glycosylation, by substitution of threonine 194 with alanine, eliminated oleic acid-mediated stimulation of apoE secretion. These results indicate that oleic acid increases apoE secretion from macrophages at a locus involving post-translational glycosylation.

show abstract

“…In contrast to the situation in endothelial cells, in megakaryocytes and in osteosarcoma cells constitutive binding of Sp1 and/or Sp3 was necessary for basal as well as for phorbol ester-induced transcription of the PDGF-B gene. Increased binding of Sp1 to its respective recognition sites was reported as a further mechanism by which Sp1 mediates enhanced gene expression, for instance in PDGF-induction of the human low density lipoprotein receptor gene (Basheeruddin et al, 1995) and in phorbol ester-induction of the human platelet thromboxane receptor gene (D'Angelo et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Sp1 recognition sites in the proximal promoter of the human vascular endothelial growth factor gene are essential for platelet-derived growth factor-induced gene expression

Finkenzeller

Sparacio

Technau³

et al. 1997

Oncogene

182

170

View full text Add to dashboard Cite

Stimulation of NIH3T3 cells with platelet-derived growth factor (PDGF)-BB enhances expression of vascular endothelial growth factor (VEGF), an endothelial cell-speci®c mitogen and a key mediator of tumor angiogenesis. Here, we identi®ed cis-acting VEGF promoter elements and trans-acting factors which are involved in PDGF-stimulated VEGF expression. By 5'-deletion and transient transfection analysis, a G+C-rich region at 785 to 750 of the human VEGF promoter was shown to be necessary and su cient for both PDGF inducible and basal expression. The region contains three potential recognition sites for Sp1 transcription factors, which overlap with two Egr-1 sites. Mutations that abolish the ability of Sp1 to interact with the VEGF promoter element also abrogate expression induced by PDGF. Mutations of the potential Egr-1 binding sites did not a ect PDGF responsiveness. Gel shift and antibody supershift analyses showed that Sp1 and Sp3 interact constitutively with the VEGF promoter element. Our data strongly suggest that enhanced VEGF gene expression in PDGF-induced NIH3T3 cells is mediated by Sp1 and/or Sp3 transcription factors bound to the 785 to 750 promoter region of the VEGF gene.

show abstract

Platelet-Derived Growth Factor Enhances Sp1 Binding to the LDL Receptor Gene

Cited by 10 publications

References 36 publications

CCAAT/Enhancer-binding Protein β Inhibits Proliferation in Monocytic Cells by Affecting the Retinoblastoma Protein/E2F/Cyclin E Pathway but Is Not Directly Required for Macrophage Morphology

CCAAT/Enhancer-binding Protein β Inhibits Proliferation in Monocytic Cells by Affecting the Retinoblastoma Protein/E2F/Cyclin E Pathway but Is Not Directly Required for Macrophage Morphology

Oleic Acid Modulates the Post-translational Glycosylation of Macrophage ApoE to Increase Its Secretion

Sp1 recognition sites in the proximal promoter of the human vascular endothelial growth factor gene are essential for platelet-derived growth factor-induced gene expression

Contact Info

Product

Resources

About