Imatinib mesylate affects extracellular ATP catabolism and expression of NTPDases in a chronic myeloid leukemia cell line

Purinergic Signalling - Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm, characterized by the occurrence of the t(9;22)(q34;q11) translocation. First-line therapy for CML consists...     

Adenosine uptake is the major effector of extracellular ATP toxicity in human cervical cancer cells

In cervical cancer, HPV infection and disruption of mechanisms involving cell growth, differentiation, and apoptosis are strictly linked with tumor progression and invasion. Tumor microenvironment is ATP and adenosine rich, suggesting a role for purinergic signaling in cancer cell growth and death. Here we investigate the effect of extracellular ATP on human cervical cancer cells. We find that extracellular ATP itself has a small cytotoxic effect, whereas adenosine formed from ATP degradation by ectonucleotidases is the main factor responsible for apoptosis induction. The level of P2×7 receptor seemed to define the main cytotoxic mechanism triggered by ATP, since ATP itself eliminated a small subpopulation of cells that express high P2×7 levels, probably through its activation. Corroborating these data, blockage or knockdown of P2×7 only slightly reduced ATP cytotoxicity. On the other hand, cell viability was almost totally recovered with dipyridamole, an adenosine transporter inhibitor. Moreover, ATP-induced apoptosis and signaling—p53 increase, AMPK activation, and PARP cleavage—as well as autophagy induction were also inhibited by dipyridamole. In addition, inhibition of adenosine conversion into AMP also blocked cell death, indicating that metabolization of intracellular adenosine originating from extracellular ATP is responsible for the main effects of the latter in human cervical cancer cells.     

Long-term socio-ecological research (LTSER) for biodiversity protection – A complex systems approach for the study of dynamic human–nature interactions

Recently, the long-term ecological research (LTER) program in the US was evaluated. In its 20-year review report, the National Science Foundation recognizes the achievements of the past and specifies guidance for future development. Among other aspects, research activities of the next decade should concentrate on a new core area: biological diversity, and, to inform environmental policy on the interrelationships and reciprocal impacts of ecological and human systems, LTER is requested “to partner with social scientists” at all existing or newly selected research sites (http://www.nsf.gov/od/lpa/news/02/pr0265.htm). In Europe, LTER activities head in the same direction. To create durable integration of European biodiversity research capacity and to address biodiversity policy needs, long-term socio-ecological research (LTSER) sites should serve as real-world laboratories for interdisciplinary and policy relevant research (http://www.lter-europe.ceh.ac.uk and www.alter-net.info). In this paper, we explore how LTER could meet the challenges of the future: the increase of knowledge on issues of biological diversity and of partnership approaches among the natural and social sciences in common research facilities – the LTSER sites.Regarding biological diversity we explore, in particular, the advantages for improving: (1) ecological-economic modelling, a powerful technique for analysing complex human–nature interaction, (2) the design of choice experiments, a rather new evaluation method for assessing the benefits of conservation and (3) the understanding of biodiversity as complex social dilemma. Regarding the issue of research collaboration, we focus on the geographical scale of LTSER sites and, on a more general level, on the demands of research management in terms of project design, common knowledge and organisation of research teams.