Progesterone Receptor Activation of Extranuclear Signaling Pathways in Regulating p53 Expression in Vascular Endothelial Cells

Hsu, Sung Po; Lee, Wen Sen

doi:10.1210/me.2010-0424

Cited by 29 publications

(41 citation statements)

References 29 publications

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“…Previously, we have demonstrated that ERK is the downstream molecule of the Src involved in the progesterone-induced upregulation of p53 in HUVEC [12]. In the present study, we show that FA treatment increased the levels of p-ERK 1/2 (Fig.…”

Section: Discussionsupporting

confidence: 76%

“…Expression of p21 is inducible by wildtype p53 but not mutant p53 [23]. Several studies have shown that expression of p53 in the cell can induce cell growth arrest through transcriptional activation of p21 [12,25,26]. In this study, we show that FA increased the levels of p53 protein (Fig.…”

Section: Discussionsupporting

confidence: 57%

“…For transient transfection of the indicated constructs into HUVEC, jetPEI-HUVEC transfection reagent (Polyplus Transfection, Bioparc, France) was used and the transfection was performed as previously described [11,12].…”

Section: Cell Transfectionmentioning

confidence: 99%

“…To examine the effect of FA on nuclear translocation of NF-jB (p65), the NE-PER nuclear and cytoplasmic extraction reagents (Thermo Fisher Scientific, Rockford, IL) was used and the extraction was performed as previously described [12].…”

Section: Nuclear Extractionmentioning

confidence: 99%

“…To examine whether NF-jB is bound onto the p53 promoter, the ChIP assay was performed as previously described [12].…”

Section: Chromatin Immunoprecipitation (Chip) Assaymentioning

confidence: 99%

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Folic acid inhibits endothelial cell proliferation through activating the cSrc/ERK 2/NF-κB/p53 pathway mediated by folic acid receptor

Lin

Lee

et al. 2012

Angiogenesis

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Folate is important for normal cell division. Folate deficiency has been implicated in various diseases, including atherosclerosis, neural tube defects, and cancer. However, the effect of folate on angiogenesis was unclear. The aim of this study was to investigate the anti-angiogenic action of folic acid (FA). FA (0-10 μmol/L) concentration-dependently decreased DNA synthesis and proliferation in cultured human umbilical venous endothelial cells (HUVEC). Western blot analyses demonstrated that the levels of p21, p27 and p53 protein in HUVEC were increased by FA. The FA-inhibited [3H]thymidine incorporation was completely blocked when the expressions of p21 and p27 were knocked-down together. Knock-down of p53 prevented the FA-induced increases in p21 and p27 protein level. The levels of phosphorylated Src (p-Src) and p-Src-FA receptor (FR) complex in HUVEC were increased by FA. Knock-down of FR reduced the FA-induced increases of p-Src and p53. The FA-induced increases of p21, p27 and p53 protein levels were abolished when cSrc was knocked-down. FA also increased NF-κB nuclear translocation and binding onto the p53 promoter. The FA-induced up-regulation of the p53 promoter activity was prevented by knocked-down of ERK. Matrigel angiogenesis assay in mice demonstrate the anti-angiogenic effect of FA in vivo. In conclusion, our data indicate that FA bound to FR in HUVEC, subsequently activated the cSrc/ERK 2/NF-κB/p53 signaling pathway, which in turn up-regulated the expression of p21 and p27, and finally resulted in cell cycle arrest at the G0/G1 phase. In the present study, we uncover a completely novel role of FA for anti-angiogenesis.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionsupporting

confidence: 57%

Section: Cell Transfectionmentioning

confidence: 99%

Section: Nuclear Extractionmentioning

confidence: 99%

“…To examine whether NF-jB is bound onto the p53 promoter, the ChIP assay was performed as previously described [12].…”

Section: Chromatin Immunoprecipitation (Chip) Assaymentioning

confidence: 99%

See 3 more Smart Citations

Folic acid inhibits endothelial cell proliferation through activating the cSrc/ERK 2/NF-κB/p53 pathway mediated by folic acid receptor

Lin

Lee

et al. 2012

Angiogenesis

Self Cite

View full text Add to dashboard Cite

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Effect of dietary administration of Chinese torreya nut on reproductive function in ICR female mice and its possible mechanism of action

et al. 2023

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Chinese torreya nut (Torreya grandis cv. Merrillii) is a unique edible nut that grows in China, which is known for its ability to reduce blood lipids, prevent blood sclerosis, and coronary heart disease. However, its effect on reproduction is not well understood. In this study, the comprehensive effects of Chinese torreya nut on the sex hormones and endometrium in female mice and their uterine expression profiles were investigated. Here, feeding of mice with Chinese torreya nut resulted in a decrease in uterine coefficients and serum progesterone levels, thickening of the endometrium, and an increase in estrogen levels. The enrichment analyses indicated that the differentially expressed genes between the Chinese torreya nut addition and control mice were enriched in NOD‐like receptor signaling pathway, complement and coagulation cascades and p53 pathway. Quantitative real time PCR and western blot results showed that there were significant differences in the transcripts and protein expression of estrogen receptor alpha and progestogen receptor associated with G protein coupled estrogen receptor. These findings suggest that Chinese torreya nut may have a potentially beneficial effect on coordinating uterine contractions in mice, rendering it a promising functional food.

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Progesterone Inhibits Endothelial Cell Migration Through Suppression of the Rho Activity Mediated by cSrc Activation

Lee

Lin

Huo

et al. 2015

J of Cellular Biochemistry

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We previously showed that progesterone (P4) could inhibit the proliferation of human umbilical venous endothelial cells (HUVECs) through the p53-dependent pathway. In the present study, we further demonstrated that P4 at physiologic levels (5-500 nM) concentration-dependently inhibited migration of HUVECs. This effect was blocked by pre-treatment with the P4 receptor (PR) agonist-antagonist, RU486, suggesting that the P4-induced migration inhibition in HUVECs was through the PR-mediated signaling pathway. Western blot analyses demonstrated that the levels of RhoA and Rac-1 protein were reduced in the P4-treated HUVECs. P4 also inhibited the membrane translocation of RhoA and Rac-1 protein. Moreover, the P4-induced migration inhibition in HUVECs was prevented by over-expression of the constitutively active RhoA construct (RhoA V14). However, pre-treatment with the ROCK (a kinase associated with RhoA for transducing RhoA signaling) inhibitor, Y27632, abolished the over-expression of RhoA-induced prevention effect on the P4-induced migration inhibition in HUVECs. These data suggest that the inhibition of Rho GTPases might account for the P4-induced migration inhibition of HUVECs. Pre-treatment with the cSrc inhibitor, PP2, prevented the P4-induced migration inhibition in HUVEC. The levels of phosphorylated focal adhesion kinase (FAK) and paxillin protein were also decreased by P4 treatment. Taken together, these results suggest that suppression of the Rho-mediated pathway might be involved in the signal transduction leading to the inhibition of cell migration caused by P4 in HUVECs.

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Progesterone Receptor Activation of Extranuclear Signaling Pathways in Regulating p53 Expression in Vascular Endothelial Cells

Cited by 29 publications

References 29 publications

Folic acid inhibits endothelial cell proliferation through activating the cSrc/ERK 2/NF-κB/p53 pathway mediated by folic acid receptor

Folic acid inhibits endothelial cell proliferation through activating the cSrc/ERK 2/NF-κB/p53 pathway mediated by folic acid receptor

Effect of dietary administration of Chinese torreya nut on reproductive function in ICR female mice and its possible mechanism of action

Progesterone Inhibits Endothelial Cell Migration Through Suppression of the Rho Activity Mediated by cSrc Activation

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