The kinase p38 Regulates Peroxisome Proliferator Activated Receptor-γ in Human Trophoblasts

Schild, R. L.; Sonnenberg-Hirche, Christina; Schaiff, W. Timothy; Bildirici, İbrahim; Nelson, D. Michael; Sadovsky, Yoel

doi:10.1016/j.placenta.2005.01.012

Cited by 31 publications

(22 citation statements)

References 73 publications

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“…It is known that p38 signaling participates in the regulation of apoptotic cell death by upregulating the expression of proapoptotic genes, such as Fas ligand, PPARG2, and GADD153 (29)(30)(31)(32). Moreover, p38 is also involved in the negative regulation of cell growth, as it represses cyclin D1 expression and activates p27 (33,34).…”

Section: Discussionmentioning

confidence: 99%

CEBPD Reverses RB/E2F1-Mediated Gene Repression and Participates in HMDB-Induced Apoptosis of Cancer Cells

Pan

et al. 2010

Clinical Cancer Research

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Purpose: Recent evidence indicates that a tumor suppressor gene CEBPD (CCAAT/enhancer-binding protein delta) is downregulated in many cancers including cervical cancer, which provides a therapeutic potential associated with its reactivation. However, little is known for CEBPD activators and the effect of reactivation of CEBPD transcription upon anticancer drug treatment. In this study, we identified a novel CEBPD activator, 1-(2-hydroxy-5-methylphenyl)-3-phenyl-1,3-propanedione (HMDB). The purpose of this study is to characterize the mechanism of HMDB-induced CEBPD activation and its potential effect in cancer therapy.Experimental Design: Methylation-specific PCR assay, reporter assay, and chromatin immunoprecipitation (ChIP) assay were performed to dissect the signaling pathway of HMDB-induced CEBPD transcription. Furthermore, a consequence of HMDB-induced CEBPD expression was linked with E2F1 and retinoblastoma (RB), which discloses the scenario of CEBPD, E2F1, and RB bindings and transcriptional regulation on the promoters of proapoptotic genes, PPARG2 and GADD153. Finally, the anticancer effect of HMDB was examined in xenograft mice.Results: We demonstrate that CEBPD plays an essential role in HMDB-mediated apoptosis of cancer cells. HMDB up-regulates CEBPD transcription through the p38/CREB pathway, thus leading to transcriptional activation of PPARG2 and GADD153. Furthermore, increased level of CEBPD attenuates E2F1-induced cancer cell proliferation and partially rescues RB/E2F1-mediated repression of PPARG2 and GADD153 transcription. Moreover, HMDB treatment attenuates the growth of A431 xenografts in severe combined immunodeficient mice mice.Conclusions: These results clearly demonstrate that HMDB kills cancer cells through activation of CEBPD pathways and suggest that HMDB can serve as a superior chemotherapeutic agent with limited potential for adverse side effects. Clin Cancer Res; 16(23); 5770-80. Ó2010 AACR.

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Section: Discussionmentioning

confidence: 99%

CEBPD Reverses RB/E2F1-Mediated Gene Repression and Participates in HMDB-Induced Apoptosis of Cancer Cells

Pan

et al. 2010

Clinical Cancer Research

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“…Previous experiments in our laboratory and others have shown that active p38 MAPK is required for PPAR␥ activity and expression (13)(14)(15). We therefore hypothesized that inhibition of p38 MAPK might diminish fatty acid uptake by trophoblasts.…”

Section: P38 Mapk Regulates Fatty Acid Uptake and Transporter Expressmentioning

confidence: 92%

“…The concentrations of GW1929 and LG268 used were the lowest concentration to induce maximal trophoblast differentiation as measured by human chorionic gonadotropin secretion (15) (data not shown). The concentration of p38 MAPK inhibitors used was as previously described (15).…”

Section: Cell Culturesmentioning

confidence: 99%

“…This process is accompanied by an increase in accumulation of neutral lipids, particularly in syncytiotrophoblasts (10). Interestingly, the p38 MAPK, which is also essential for development of the murine placental labyrinth (11,12), regulates the transcriptional activity of PPAR␥ (13)(14)(15). Inhibition of p38 MAPK activity leads to inhibition of PPAR␥-induced cellular differentiation of trophoblasts, preadipocytes, and macrophages, and activation of p38 MAPK potentiates PPAR␥ activity (13,14).…”

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confidence: 99%

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Peroxisome Proliferator-Activated Receptor-γ and Retinoid X Receptor Signaling Regulate Fatty Acid Uptake by Primary Human Placental Trophoblasts

Schaiff

Bildirici

Cheong

et al. 2005

The Journal of Clinical Endocrinology & Metabolism

148

101

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“…The PPARs represent a link between energy metabolism and reproduction implicated in early pregnancy development, including implantation, placentation, and trophoblast differentiation ( Fig. 1) (26,81,118,124). A conserved structural homology is present in all distinct PPAR isoforms, particularly in the DNA-binding domain and ligand-binding domain.…”

Section: The Ppar Family and Its Role In Reproductionmentioning

confidence: 99%

The peroxisome proliferator-activated receptors under epigenetic control in placental metabolism and fetal development

Lendvai

Deutsch

Plösch

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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The kinase p38 Regulates Peroxisome Proliferator Activated Receptor-γ in Human Trophoblasts

Cited by 31 publications

References 73 publications

CEBPD Reverses RB/E2F1-Mediated Gene Repression and Participates in HMDB-Induced Apoptosis of Cancer Cells

CEBPD Reverses RB/E2F1-Mediated Gene Repression and Participates in HMDB-Induced Apoptosis of Cancer Cells

Peroxisome Proliferator-Activated Receptor-γ and Retinoid X Receptor Signaling Regulate Fatty Acid Uptake by Primary Human Placental Trophoblasts

The peroxisome proliferator-activated receptors under epigenetic control in placental metabolism and fetal development

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