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The role of PPARγ in TBBPA-mediated endocrine disrupting effects in human choriocarcinoma JEG-3 cells.

Honkisz E, Wójtowicz AK - Mol. Cell. Biochem. (2015)

Bottom Line: Our results showed that after TBBPA treatment at 10 nM and 10 µM, PPARγ protein expression increased in a time-dependent manner until 48 h and then slightly decreased at 72 h but was still above the control level.Finally, in the present study, we demonstrated that TBBPA at all of the tested doses significantly increased caspase-3 activity compared with that of the vehicle control.These results showed the up-regulation of PPARγ protein expression after TBBPA exposure in human placental cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal Biotechnology, University of Agriculture, Rędzina 1B, 30-248, Kraków, Poland.

ABSTRACT
The goal of the present study was to investigate the action of TBBPA on PPARγ protein expression in vitro in human choriocarcinoma-derived placental JEG-3 cells. We also analyzed TBBPA for its action on placental secretion of progesterone and β-hCG, cell viability, and apoptosis. Our results showed that after TBBPA treatment at 10 nM and 10 µM, PPARγ protein expression increased in a time-dependent manner until 48 h and then slightly decreased at 72 h but was still above the control level. This alteration in PPARγ protein expression was accompanied by a decreased β-hCG level. Interestingly, co-treatment with the PPARγ antagonist GW9662 reversed the TBBPA-mediated changes in PPARγ protein expression but, according to β-hCG secretion, potentiated an inhibitory effect of TBBPA. Additionally, in our study, we assessed the ability of TBBPA to increase progesterone levels in JEG-3 cells compared with those of controls. Finally, in the present study, we demonstrated that TBBPA at all of the tested doses significantly increased caspase-3 activity compared with that of the vehicle control. The apoptotic action of TBBPA was also confirmed by Hoechst 33342 staining. These results showed the up-regulation of PPARγ protein expression after TBBPA exposure in human placental cells. Although co-treatment with antagonist of PPARγ reversed the TBBPA-mediated increase in this protein expression and restored it to the control level, it did not reverse the effect on β-hCG secretion. This indicated that the mechanism of TBBPA-induced changes in β-hCG secretion is PPARγ-independent.

No MeSH data available.


Related in: MedlinePlus

Time- and dose-dependent effect of increasing concentrations of TBBPA on JEG-3 cells viability (line graph) and β-hCG secretion (bar graph). Each point represents the mean ± SEM of three independent experiments, each of which consisted of ten replicates per treatment group. Data indicated with *p < 0.05; ***p < 0.001 (β-hCG secretion) and ###p < 0.001 (LDH release) reflects statistically significant differences between control and experimental groups
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Fig4: Time- and dose-dependent effect of increasing concentrations of TBBPA on JEG-3 cells viability (line graph) and β-hCG secretion (bar graph). Each point represents the mean ± SEM of three independent experiments, each of which consisted of ten replicates per treatment group. Data indicated with *p < 0.05; ***p < 0.001 (β-hCG secretion) and ###p < 0.001 (LDH release) reflects statistically significant differences between control and experimental groups

Mentions: TBBPA at nanomolar and micromolar concentrations significantly decreased β-hCG release by JEG-3 cells at all culture time points (24–72 h) (Fig. 4). TBBPA-induced decrease in β-hCG secretion ranged from 15 to 37 % compared to control (vehicle-treated) cells. The highest TBBPA dose (100 μM) showed a strong cytotoxic effect as demonstrated by an increase in LDH release and a low undetectable medium level of β-hCG.Fig. 4


The role of PPARγ in TBBPA-mediated endocrine disrupting effects in human choriocarcinoma JEG-3 cells.

Honkisz E, Wójtowicz AK - Mol. Cell. Biochem. (2015)

Time- and dose-dependent effect of increasing concentrations of TBBPA on JEG-3 cells viability (line graph) and β-hCG secretion (bar graph). Each point represents the mean ± SEM of three independent experiments, each of which consisted of ten replicates per treatment group. Data indicated with *p < 0.05; ***p < 0.001 (β-hCG secretion) and ###p < 0.001 (LDH release) reflects statistically significant differences between control and experimental groups
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4589557&req=5

Fig4: Time- and dose-dependent effect of increasing concentrations of TBBPA on JEG-3 cells viability (line graph) and β-hCG secretion (bar graph). Each point represents the mean ± SEM of three independent experiments, each of which consisted of ten replicates per treatment group. Data indicated with *p < 0.05; ***p < 0.001 (β-hCG secretion) and ###p < 0.001 (LDH release) reflects statistically significant differences between control and experimental groups
Mentions: TBBPA at nanomolar and micromolar concentrations significantly decreased β-hCG release by JEG-3 cells at all culture time points (24–72 h) (Fig. 4). TBBPA-induced decrease in β-hCG secretion ranged from 15 to 37 % compared to control (vehicle-treated) cells. The highest TBBPA dose (100 μM) showed a strong cytotoxic effect as demonstrated by an increase in LDH release and a low undetectable medium level of β-hCG.Fig. 4

Bottom Line: Our results showed that after TBBPA treatment at 10 nM and 10 µM, PPARγ protein expression increased in a time-dependent manner until 48 h and then slightly decreased at 72 h but was still above the control level.Finally, in the present study, we demonstrated that TBBPA at all of the tested doses significantly increased caspase-3 activity compared with that of the vehicle control.These results showed the up-regulation of PPARγ protein expression after TBBPA exposure in human placental cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal Biotechnology, University of Agriculture, Rędzina 1B, 30-248, Kraków, Poland.

ABSTRACT
The goal of the present study was to investigate the action of TBBPA on PPARγ protein expression in vitro in human choriocarcinoma-derived placental JEG-3 cells. We also analyzed TBBPA for its action on placental secretion of progesterone and β-hCG, cell viability, and apoptosis. Our results showed that after TBBPA treatment at 10 nM and 10 µM, PPARγ protein expression increased in a time-dependent manner until 48 h and then slightly decreased at 72 h but was still above the control level. This alteration in PPARγ protein expression was accompanied by a decreased β-hCG level. Interestingly, co-treatment with the PPARγ antagonist GW9662 reversed the TBBPA-mediated changes in PPARγ protein expression but, according to β-hCG secretion, potentiated an inhibitory effect of TBBPA. Additionally, in our study, we assessed the ability of TBBPA to increase progesterone levels in JEG-3 cells compared with those of controls. Finally, in the present study, we demonstrated that TBBPA at all of the tested doses significantly increased caspase-3 activity compared with that of the vehicle control. The apoptotic action of TBBPA was also confirmed by Hoechst 33342 staining. These results showed the up-regulation of PPARγ protein expression after TBBPA exposure in human placental cells. Although co-treatment with antagonist of PPARγ reversed the TBBPA-mediated increase in this protein expression and restored it to the control level, it did not reverse the effect on β-hCG secretion. This indicated that the mechanism of TBBPA-induced changes in β-hCG secretion is PPARγ-independent.

No MeSH data available.


Related in: MedlinePlus