7 research outputs found
Molecular Interactions of Prodiginines with the BH3 Domain of Anti-Apoptotic Bcl-2 Family Members
Prodigiosin and obatoclax, members of the prodiginines family, are small molecules with anti-cancer properties that are
currently under preclinical and clinical trials. The molecular target(s) of these agents, however, is an open question.
Combining experimental and computational techniques we find that prodigiosin binds to the BH3 domain in some BCL-2
protein families, which play an important role in the apoptotic programmed cell death. In particular, our results indicate
a large affinity of prodigiosin for MCL-1, an anti-apoptotic member of the BCL-2 family. In melanoma cells, we demonstrate
that prodigiosin activates the mitochondrial apoptotic pathway by disrupting MCL-1/BAK complexes. Computer simulations
with the PELE software allow the description of the induced fit process, obtaining a detailed atomic view of the molecular
interactions. These results provide new data to understand the mechanism of action of these molecules, and assist in the
development of more specific inhibitors of anti-apoptotic BCL-2 proteins.Spanish government and the European Union (FIS-PI10/00338) and from the ERC-2009-Adg
25027-PELE European project
Severe traumatic injury during long duration spaceflight: Light years beyond ATLS
Traumatic injury strikes unexpectedly among the healthiest members of the human population, and has been an inevitable companion of exploration throughout history. In space flight beyond the Earth's orbit, NASA considers trauma to be the highest level of concern regarding the probable incidence versus impact on mission and health. Because of limited resources, medical care will have to focus on the conditions most likely to occur, as well as those with the most significant impact on the crew and mission. Although the relative risk of disabling injuries is significantly higher than traumatic deaths on earth, either issue would have catastrophic implications during space flight. As a result this review focuses on serious life-threatening injuries during space flight as determined by a NASA consensus conference attended by experts in all aspects of injury and space flight