A novel mechanism of resistance to α-difluoromethylornithine induced by cycloheximide. Growth with abnormally low levels of putrescine and spermidine

Treatment of the chemically transformed fibroblasts BP-A31 and other cell lines with low concentrations of cycloheximide (CHM) for 72 h followed by the removal of the protein synthesis inhibitor leads to the proliferation of α-difluoromethylornithine (DFMO)-resistant phenotypes. These drug-resistant cells contain almost no ornithine decarboxylase (ODC) activity and concomitantly very low levels of putrescine and spermidine. Southern blot analysis and measurements of ODC activity and intracellular polyamine levels showed that the described mechanism of inducing resistance to DFMO triggered by CHM does not involve ODC gene amplification, altered transport of the drug or reduced affinity of the enzyme for DFMO. © 1986.Fil:Medrano, E.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Burrone, O.R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Ferrer, M.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Algranati, I.D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Sphingosylphosphorylcholine-induced ERK activation inhibits melanin synthesis in human melanocytes

Sphingosylphosphorylcholine (SPC) is emerging as a potent signaling-lipid mediator. In this study, we investigated the effects of SPC on melanogenesis using cultured human melanocytes. Our results show that SPC significantly inhibits melanin synthesis in a concentration-dependent manner, and further that it reduces the activity of tyrosinase, the rate-limiting melanogenic enzyme. SPC treatment was also found to induce short-thick dendrites in human melanocytes, but not to reduce tyrosinase activity in a cell-free system, whereas kojic acid directly inhibited tyrosinase. These results suggest that SPC reduces pigmentation by indirectly regulating tyrosinase. In further experiments, SPC was found to downregulate microphthalmia-associated transcription factor (MITF) and tyrosinase, and Western blotting showed that SPC induces the activations of extracellular signal-regulated kinase (ERK) and 90 kDa ribosomal S6 kinase (RSK-1). Moreover, the specific ERK pathway inhibitor, PD98059, blocked the hypopigmentation effect of SPC, and abrogated the SPC-mediated downregulation of MITF. These results suggest that the ERK pathway is involved in the melanogenic signaling cascade, and that ERK activation by SPC reduces melanin synthesis via MITF downregulation

Globalization and the transformation of the national political space: six European countries compared

This article starts from the assumption that the current process of globalization or denationalization leads to the formation of a new structural conflict in Western European countries, opposing those who benefit from this process against those who tend to lose in the course of the events. The structural opposition between globalization 'winners' and 'losers' is expected to constitute potentials for political mobilization within national political contexts, the mobilization of which is expected to give rise to two intimately related dynamics: the transformation of the basic structure of the national political space and the strategic repositioning of the political parties within the transforming space. The article presents several hypotheses with regard to these two dynamics and tests them empirically on the basis of new data concerning the supply side of electoral politics from six Western European countries (Austria, Britain, France, Germany, the Netherlands and Switzerland). The results indicate that in all the countries, the new cleavage has become embedded into existing two-dimensional national political spaces, that the meaning of the original dimensions has been transformed, and that the configuration of the main parties has become triangular even in a country like France