Abstract
Active oxygen, produced by cultured cells following stimulation with various growth factors, seems to be involved in signal transduction leading to cellular responses such as gene expression and growth modulation. In the present study, the intracellular oxidation state was measured in immortalized human endothelial cells (ECV304) after treatment with tumor necrosis factor (TNF)α, using a fluorescent dye and a laser-scanning confocal microscope. The intracellular oxidation state was increased 60 min after the addition of TNFα, and this increase was abolished by a radical scavenger, N-acetylcysteine (NAC), which is also a precursor of glutathione, and by pyrrolidine dithiocarbamate (PDTC). TNFα increased the steady state level of urokinase-type plasminogen activator (uPA), and NAC inhibited this increase at a dose that also inhibited the increase in the intracellular oxidation state. PDTC, on the other hand, did not affect the induction of the uPA gene by TNFα. These results suggest that intracellular glutathione level rather than the oxidation state is necessary for the induction of the uPA gene by TNFα.
Similar content being viewed by others
References
Meier, B., Radeke, H. S., Selle, S., Younes, N., Sie, H., Reshc, K., and Habermehl, G. G., Biochem. J.263 (1989) 539.
Matsubaram, T., and Ziff, M., J. Immun.137 (1986) 3295.
Shibanuma, M., Kuroki, T., and Nose, K., Cell Growth Diff.2 (1991) 583.
Shirak, A. A., Beavis, A. J., and Robertson, F. M., Carcinogenesis12 (1991) 91.
Baustista, A. P., and Spitzer, J. J., Am. J. Physiol.259 (1990) G907.
Schreck, R., Rieber, P., and Baeuerle, P. A., EMBO J.10 (1991) 2247.
Guy, G. R., Cairns, J., Ng, S. B., and Tan, Y. H., J. biol. Chem.268 (1993) 2141.
Shibanuma, M., Kuroki, T., and Nose, K., Biochem. biophys. Res. Commun.187 (1992) 1418.
Ohba, M., Shibanuma, M., Kuroki, T., and Nose, K., J. Cell Biol.126 (1994) 1079.
Satriano, J. A., Shuldiner, M. S., Hora, K., Xing, Y., Shan, Z., and Schlondrff, D., J., clin. Invest.92 (1993) 1564.
DeForge, L. E., Preston, A. M., Takeuchi, E., Kenny, J., Boxter, L. A., and Remick, D. G., J. biol. Chem.268 (1993) 25568.
Shibanuma, M., Kuroki, T., and Nose, K., Oncogene5 (1990) 1025.
Nose, K., Shibanuma, M., Kikuchi, K., Kageyama, H., Sakiyama, S., and Kuroki, T., Eur. J. Biochem.201 (1991) 99.
Marshall, B. C., Xu, Q-P., Rao, N. V., Brown, B. R., and Hoidal, J. R., J. Biol. Chem.267 (1992) 11462.
Carlsen, S. A., Ramshaw, I. A., and Warrington, R. C., Cancer Res.44 (1984) 3012.
Nerlov, C., Rørth, P., Blasi, F., and Johnsen, M., Oncogene6 (1991) 1583.
Nerlov, C., De Cesare, D., Pergola, F., Caracciolo, A., Blasi, F., Johnsen, M., and Verde, P., EMBO J.11 (1992) 4573.
Abate, C., Patel, L., Rauscher, F. J. III., and Curran, T., Science, Wash.249 (1990) 1157.
Takahashi, K., Sawasaki, Y., Hata, J., Mukai, K., and Goto, T., In vitro cell. dev. biol.25 (1990) 265.
Szejda, P., Parce, J. W., Seeds, M. S., and Bass, D. A., J. Immun.133 (1984) 3303.
Shibanuma, M., Kuroki, T., and Nose, K. J. biol. Chem.267 (1992) 10219.
Riccio, A., Grimaldi, G., Verde, P., Sebastio, G., Boast, S., and Blasi, F. Nucl. Acids Res.13 (1985) 2759.
Lewis, S. A., Lee, M. G.-S., and Cowan, N. J., J. Cell. Biol.101 (1985) 852.
Meyer, M., Schreck, R., and Baeuerle, P. A., EMBO J.12 (1993) 1005.
Staal, F. J. T., Roederer, M., Herzenberg, L. A., and Herzenberg, L. A., Proc. natl Acad. Sci. USA.87 (1989) 9943.
Gilbert, H. R., McLean, V., and Lean, M., Adv. Enzyme Regul.63 (1990) 69.
Gillis, P., and Malter, J. S., J. biol. Chem.266 (1991) 3172.
Malter, J. S., and Hong, Y., J. biol. Chem.266 (1991) 3167.
Sappino, A.-P., Busso, N., Berlin, D., and Vassalli, J.-D., Cancer Res.47 (1987) 4043.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Egawa, K., Yoshiwara, M. & Nose, K. Effect of radical scavengers on TNFα-mediated activation of the uPA in cultured cells. Experientia 50, 958–962 (1994). https://doi.org/10.1007/BF01923487
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF01923487