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Adverse effects of reduced oxygen tension on the proliferative capacity of rat kidney and insulin-secreting cell lines involve DNA damage and stress responses.

Chen JH, Jones RH, Tarry-Adkins J, Smith NH, Ozanne SE - Exp. Cell Res. (2008)

Bottom Line: We observed that the proliferative capacity of the rat cell lines NRK and INS-1 was inhibited when cultured under 3% oxygen as compared to 20% oxygen.Although Sirt1 was up-regulated in both cell lines by 3% oxygen the effects on antioxidant enzymes (MnSOD, CuZnSOD and catalase) were cell line specific.HO-1 expression can be readily induced by exposure to hydrogen peroxide in culture.

View Article: PubMed Central - PubMed

Affiliation: Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK. jhc36@cam.ac.uk

ABSTRACT
Standard cell culture conditions do not reflect the physiological environment in terms of oxygen tension (20% vs 3%). The effects of lowering oxygen tension on cell proliferation in culture can be beneficial as well as detrimental depending on the cell line studied, but the molecular mechanism underlying such effects is not fully understood. We observed that the proliferative capacity of the rat cell lines NRK and INS-1 was inhibited when cultured under 3% oxygen as compared to 20% oxygen. Suppression of proliferation in NRK cells was accompanied by induction of DNA double strand breaks whereas in INS-1 cells it was accompanied by up-regulation of p53 and p27. Although Sirt1 was up-regulated in both cell lines by 3% oxygen the effects on antioxidant enzymes (MnSOD, CuZnSOD and catalase) were cell line specific. Marked up-regulation of heme oxygenase-1 (HO-1) was detected in both NRK and INS-1 cells when cultured in 3% oxygen. HO-1 expression can be readily induced by exposure to hydrogen peroxide in culture. These results suggest that reduced oxygen tension suppresses the proliferative capacity of these two cell lines through a stress response that is similar to an oxidative stress response but the molecular events that lead to the reduced cell proliferation are cell line specific.

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Proliferation of NRK and INS-1 cells cultured under 3% and 20% oxygen tensions. Cells were seeded 1 × 104 cells/60 mm dish and the cell number was then counted at the indicated times. Means of three experiments are shown. Closed square, 20% O2; open square, 3% O2 (± SEM indicated by error bars).
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fig1: Proliferation of NRK and INS-1 cells cultured under 3% and 20% oxygen tensions. Cells were seeded 1 × 104 cells/60 mm dish and the cell number was then counted at the indicated times. Means of three experiments are shown. Closed square, 20% O2; open square, 3% O2 (± SEM indicated by error bars).

Mentions: Comparison of cell proliferation under 3% and 20% oxygen tensions revealed that the proliferative capacity of NRK and INS-1 was suppressed by 3% oxygen tension (Fig. 1). The suppression of cell proliferation was not apparent in the first week of culture but became increasingly significant in the subsequent 4 weeks (Fig. 1).


Adverse effects of reduced oxygen tension on the proliferative capacity of rat kidney and insulin-secreting cell lines involve DNA damage and stress responses.

Chen JH, Jones RH, Tarry-Adkins J, Smith NH, Ozanne SE - Exp. Cell Res. (2008)

Proliferation of NRK and INS-1 cells cultured under 3% and 20% oxygen tensions. Cells were seeded 1 × 104 cells/60 mm dish and the cell number was then counted at the indicated times. Means of three experiments are shown. Closed square, 20% O2; open square, 3% O2 (± SEM indicated by error bars).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2631166&req=5

fig1: Proliferation of NRK and INS-1 cells cultured under 3% and 20% oxygen tensions. Cells were seeded 1 × 104 cells/60 mm dish and the cell number was then counted at the indicated times. Means of three experiments are shown. Closed square, 20% O2; open square, 3% O2 (± SEM indicated by error bars).
Mentions: Comparison of cell proliferation under 3% and 20% oxygen tensions revealed that the proliferative capacity of NRK and INS-1 was suppressed by 3% oxygen tension (Fig. 1). The suppression of cell proliferation was not apparent in the first week of culture but became increasingly significant in the subsequent 4 weeks (Fig. 1).

Bottom Line: We observed that the proliferative capacity of the rat cell lines NRK and INS-1 was inhibited when cultured under 3% oxygen as compared to 20% oxygen.Although Sirt1 was up-regulated in both cell lines by 3% oxygen the effects on antioxidant enzymes (MnSOD, CuZnSOD and catalase) were cell line specific.HO-1 expression can be readily induced by exposure to hydrogen peroxide in culture.

View Article: PubMed Central - PubMed

Affiliation: Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK. jhc36@cam.ac.uk

ABSTRACT
Standard cell culture conditions do not reflect the physiological environment in terms of oxygen tension (20% vs 3%). The effects of lowering oxygen tension on cell proliferation in culture can be beneficial as well as detrimental depending on the cell line studied, but the molecular mechanism underlying such effects is not fully understood. We observed that the proliferative capacity of the rat cell lines NRK and INS-1 was inhibited when cultured under 3% oxygen as compared to 20% oxygen. Suppression of proliferation in NRK cells was accompanied by induction of DNA double strand breaks whereas in INS-1 cells it was accompanied by up-regulation of p53 and p27. Although Sirt1 was up-regulated in both cell lines by 3% oxygen the effects on antioxidant enzymes (MnSOD, CuZnSOD and catalase) were cell line specific. Marked up-regulation of heme oxygenase-1 (HO-1) was detected in both NRK and INS-1 cells when cultured in 3% oxygen. HO-1 expression can be readily induced by exposure to hydrogen peroxide in culture. These results suggest that reduced oxygen tension suppresses the proliferative capacity of these two cell lines through a stress response that is similar to an oxidative stress response but the molecular events that lead to the reduced cell proliferation are cell line specific.

Show MeSH
Related in: MedlinePlus