Limits...
Functional interaction between cyclooxygenase-2 and p53 in response to an endogenous electrophile.

Kumagai T, Usami H, Matsukawa N, Nakashima F, Chikazawa M, Shibata T, Noguchi N, Uchida K - Redox Biol (2014)

Bottom Line: To characterize the effect of Cox-2 expression in the cells, we established the Cox-2-overexpressing derivatives of RL34 cells by stable transfection with Cox-2 cDNA.Consistent with the Cox-2-mediated down-regulation of proteasome, a moderate reduction of the proteasome activities was observed.This proteasome dysfunction mediated by the Cox-2 overproduction was associated with the enhanced accumulation of p53 and ubiquitinated proteins, leading to the enhanced sensitivity toward electrophiles.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.

No MeSH data available.


Related in: MedlinePlus

Sensitivity of Cox-2-overexpressed cells to electrophiles. (A) HNE cytotoxicity to the control and Cox-2-overexpressed cells. One control and three Cox-2-transfected cells (clone nos. 3, 8, and 15) were examined by MTT assay for sensitivity to HNE (50 µM). (B) Time-dependent reduction of cell viability induced by HNE (50 µM) in the control transfected cells and the Cox-2-overexpressed cells (clone no. 8). (C) Electrophile cytotoxicity to the control and Cox-2-overexpressed cells. The control transfected cells and the Cox-2-overexpressed cells (clone no. 8) were examined by MTT assay for sensitivity to HNE (50 or 75 µM), butylhydroquinone (50 or 100 µM), and diethylmaleimide (500 or 750 µM) for 24 h.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4309852&req=5

f0040: Sensitivity of Cox-2-overexpressed cells to electrophiles. (A) HNE cytotoxicity to the control and Cox-2-overexpressed cells. One control and three Cox-2-transfected cells (clone nos. 3, 8, and 15) were examined by MTT assay for sensitivity to HNE (50 µM). (B) Time-dependent reduction of cell viability induced by HNE (50 µM) in the control transfected cells and the Cox-2-overexpressed cells (clone no. 8). (C) Electrophile cytotoxicity to the control and Cox-2-overexpressed cells. The control transfected cells and the Cox-2-overexpressed cells (clone no. 8) were examined by MTT assay for sensitivity to HNE (50 or 75 µM), butylhydroquinone (50 or 100 µM), and diethylmaleimide (500 or 750 µM) for 24 h.

Mentions: Finally, we examined the effect of Cox-2 overexpression on the cytotoxicity of electrophiles. One control and three Cox-2-transfected cells (clone nos. 3, 8, and 15) were examined by MTT assay for sensitivity to the cytotoxicity induced by exposure to HNE, showing that HNE (50 µM) resulted in a decrease in the MTT reduction levels to 63% of the basal levels in vector control cells and to 10% of the basal levels in Cox-2-overexpressed cells after 9 h (Fig. 8, panels A and B). Cytotoxicity induced by other electrophiles, tert-butylhydroquinone and diethylmaleate, was also enhanced in the Cox-2-overexpressed cells compared with the control cells (Fig. 8C). These results suggest that the proteasome dysfunction mediated by the Cox-2 overproduction influences cellular integrity and makes the cells sensitive to electrophiles.


Functional interaction between cyclooxygenase-2 and p53 in response to an endogenous electrophile.

Kumagai T, Usami H, Matsukawa N, Nakashima F, Chikazawa M, Shibata T, Noguchi N, Uchida K - Redox Biol (2014)

Sensitivity of Cox-2-overexpressed cells to electrophiles. (A) HNE cytotoxicity to the control and Cox-2-overexpressed cells. One control and three Cox-2-transfected cells (clone nos. 3, 8, and 15) were examined by MTT assay for sensitivity to HNE (50 µM). (B) Time-dependent reduction of cell viability induced by HNE (50 µM) in the control transfected cells and the Cox-2-overexpressed cells (clone no. 8). (C) Electrophile cytotoxicity to the control and Cox-2-overexpressed cells. The control transfected cells and the Cox-2-overexpressed cells (clone no. 8) were examined by MTT assay for sensitivity to HNE (50 or 75 µM), butylhydroquinone (50 or 100 µM), and diethylmaleimide (500 or 750 µM) for 24 h.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4309852&req=5

f0040: Sensitivity of Cox-2-overexpressed cells to electrophiles. (A) HNE cytotoxicity to the control and Cox-2-overexpressed cells. One control and three Cox-2-transfected cells (clone nos. 3, 8, and 15) were examined by MTT assay for sensitivity to HNE (50 µM). (B) Time-dependent reduction of cell viability induced by HNE (50 µM) in the control transfected cells and the Cox-2-overexpressed cells (clone no. 8). (C) Electrophile cytotoxicity to the control and Cox-2-overexpressed cells. The control transfected cells and the Cox-2-overexpressed cells (clone no. 8) were examined by MTT assay for sensitivity to HNE (50 or 75 µM), butylhydroquinone (50 or 100 µM), and diethylmaleimide (500 or 750 µM) for 24 h.
Mentions: Finally, we examined the effect of Cox-2 overexpression on the cytotoxicity of electrophiles. One control and three Cox-2-transfected cells (clone nos. 3, 8, and 15) were examined by MTT assay for sensitivity to the cytotoxicity induced by exposure to HNE, showing that HNE (50 µM) resulted in a decrease in the MTT reduction levels to 63% of the basal levels in vector control cells and to 10% of the basal levels in Cox-2-overexpressed cells after 9 h (Fig. 8, panels A and B). Cytotoxicity induced by other electrophiles, tert-butylhydroquinone and diethylmaleate, was also enhanced in the Cox-2-overexpressed cells compared with the control cells (Fig. 8C). These results suggest that the proteasome dysfunction mediated by the Cox-2 overproduction influences cellular integrity and makes the cells sensitive to electrophiles.

Bottom Line: To characterize the effect of Cox-2 expression in the cells, we established the Cox-2-overexpressing derivatives of RL34 cells by stable transfection with Cox-2 cDNA.Consistent with the Cox-2-mediated down-regulation of proteasome, a moderate reduction of the proteasome activities was observed.This proteasome dysfunction mediated by the Cox-2 overproduction was associated with the enhanced accumulation of p53 and ubiquitinated proteins, leading to the enhanced sensitivity toward electrophiles.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.

No MeSH data available.


Related in: MedlinePlus