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Effects of thapsigargin on the proliferation and survival of human rheumatoid arthritis synovial cells.

Wang H, Jia XZ, Sui CJ, Zhao YP, Mei YF, Zheng YN, Zhang ZY - ScientificWorldJournal (2014)

Bottom Line: The protein and mRNA levels of cyclin D1 decreased gradually with the increasing of thapsigargin concentration and treatment times.Moreover, the protein levels of mTORC1 downstream indicators pS6K and p4EBP-1 were reduced by thapsigargin treatment at different concentrations and times, which should be responsible for the reduced cyclin D1 expressions.Our results revealed that thapsigargin may effectively impair the cell proliferation and survival of MH7A cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology, The First Affiliated Hospital of Harbin Medical University, No. 23, Road Youzheng, Nangang District, Harbin, Heilongjiang 150001, China.

ABSTRACT
A series of experiments have been carried out to investigate the effects of different concentrations of thapsigargin (0, 0.001, 0.1, and 1 μM) on the proliferation and survival of human rheumatoid arthritis synovial cells (MH7A). The results showed that thapsigargin can block the cell proliferation in human rheumatoid arthritis synovial cells in a time- and dose-dependent manner. Results of Hoechst staining suggested that thapsigargin may induce cell apoptosis in MH7A cells in a time- and dose-dependent manner, and the percentages of cell death reached 44.6% at thapsigargin concentration of 1 μM treated for 4 days compared to the control. The protein and mRNA levels of cyclin D1 decreased gradually with the increasing of thapsigargin concentration and treatment times. Moreover, the protein levels of mTORC1 downstream indicators pS6K and p4EBP-1 were reduced by thapsigargin treatment at different concentrations and times, which should be responsible for the reduced cyclin D1 expressions. Our results revealed that thapsigargin may effectively impair the cell proliferation and survival of MH7A cells. The present findings will help to understand the molecular mechanism of fibroblast-like synoviocytes proliferations and suggest that thapsigargin is of potential for the clinical treatment of rheumatoid arthritis.

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Thapsigargin inhibits MH7A cell proliferation. Histograms showed that the cell proliferation is impaired after thapsigargin treatment (0.001, 0.1, and 1 μM) in MH7A cells, by (SRB) colorimetric assay. Results are averages of three independent experiments.
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fig1: Thapsigargin inhibits MH7A cell proliferation. Histograms showed that the cell proliferation is impaired after thapsigargin treatment (0.001, 0.1, and 1 μM) in MH7A cells, by (SRB) colorimetric assay. Results are averages of three independent experiments.

Mentions: Thapsigargin has been reported to induce cell death in several types of cells by either increasing the store-mediated calcium entry or ER stress. It has been reported that thapsigargin inhibits replication of human vascular smooth muscle cell at 10 nM concentrations [19]. To determine whether thapsigargin affects cell proliferations in MH7A cells, we quantified cell proliferation in optimal growth conditions over a four-day period using the SRB colorimetric assay. By statistical analysis, we found that thapsigargin exhibited inhibitory effect on cell replications even at 0.001 μM concentration in 2-day and 4-day groups. And higher concentrations of thapsigargin (0.1 μM and 1 μM) showed stronger inhibitory effect on cell replications than those in the control groups (Figure 1). These results suggested that thapsigargin may arrest cell proliferations in MH7A human rheumatoid arthritis synovial cells in a time- and dose-dependent manner.


Effects of thapsigargin on the proliferation and survival of human rheumatoid arthritis synovial cells.

Wang H, Jia XZ, Sui CJ, Zhao YP, Mei YF, Zheng YN, Zhang ZY - ScientificWorldJournal (2014)

Thapsigargin inhibits MH7A cell proliferation. Histograms showed that the cell proliferation is impaired after thapsigargin treatment (0.001, 0.1, and 1 μM) in MH7A cells, by (SRB) colorimetric assay. Results are averages of three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3934453&req=5

fig1: Thapsigargin inhibits MH7A cell proliferation. Histograms showed that the cell proliferation is impaired after thapsigargin treatment (0.001, 0.1, and 1 μM) in MH7A cells, by (SRB) colorimetric assay. Results are averages of three independent experiments.
Mentions: Thapsigargin has been reported to induce cell death in several types of cells by either increasing the store-mediated calcium entry or ER stress. It has been reported that thapsigargin inhibits replication of human vascular smooth muscle cell at 10 nM concentrations [19]. To determine whether thapsigargin affects cell proliferations in MH7A cells, we quantified cell proliferation in optimal growth conditions over a four-day period using the SRB colorimetric assay. By statistical analysis, we found that thapsigargin exhibited inhibitory effect on cell replications even at 0.001 μM concentration in 2-day and 4-day groups. And higher concentrations of thapsigargin (0.1 μM and 1 μM) showed stronger inhibitory effect on cell replications than those in the control groups (Figure 1). These results suggested that thapsigargin may arrest cell proliferations in MH7A human rheumatoid arthritis synovial cells in a time- and dose-dependent manner.

Bottom Line: The protein and mRNA levels of cyclin D1 decreased gradually with the increasing of thapsigargin concentration and treatment times.Moreover, the protein levels of mTORC1 downstream indicators pS6K and p4EBP-1 were reduced by thapsigargin treatment at different concentrations and times, which should be responsible for the reduced cyclin D1 expressions.Our results revealed that thapsigargin may effectively impair the cell proliferation and survival of MH7A cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology, The First Affiliated Hospital of Harbin Medical University, No. 23, Road Youzheng, Nangang District, Harbin, Heilongjiang 150001, China.

ABSTRACT
A series of experiments have been carried out to investigate the effects of different concentrations of thapsigargin (0, 0.001, 0.1, and 1 μM) on the proliferation and survival of human rheumatoid arthritis synovial cells (MH7A). The results showed that thapsigargin can block the cell proliferation in human rheumatoid arthritis synovial cells in a time- and dose-dependent manner. Results of Hoechst staining suggested that thapsigargin may induce cell apoptosis in MH7A cells in a time- and dose-dependent manner, and the percentages of cell death reached 44.6% at thapsigargin concentration of 1 μM treated for 4 days compared to the control. The protein and mRNA levels of cyclin D1 decreased gradually with the increasing of thapsigargin concentration and treatment times. Moreover, the protein levels of mTORC1 downstream indicators pS6K and p4EBP-1 were reduced by thapsigargin treatment at different concentrations and times, which should be responsible for the reduced cyclin D1 expressions. Our results revealed that thapsigargin may effectively impair the cell proliferation and survival of MH7A cells. The present findings will help to understand the molecular mechanism of fibroblast-like synoviocytes proliferations and suggest that thapsigargin is of potential for the clinical treatment of rheumatoid arthritis.

Show MeSH
Related in: MedlinePlus