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It has become increasingly clear that caspases, far from being merely cell death effectors, have a much wider range of functions within the cell. These functions are as diverse as signal transduction and cytoskeletal remodeling, and caspases are now known to have an essential role in cell proliferation, migration, and differentiation. There is also evidence that apoptotic cells themselves can direct the behavior of nearby cells through the caspase-dependent secretion of paracrine signaling factors. In some processes, including the differentiation of skeletal muscle myoblasts, both caspase activation in differentiating cells as well as signaling from apoptotic cells has been reported. Here, we review the non-apoptotic outcomes of caspase activity in a range of different model systems and attempt to integrate this knowledge.
During space missions astronauts suffer from cardiovascular deconditioning, when they are exposed to microgravity conditions. Until now, no specific drugs are available for effective countermeasures, since the underlying mechanism is not completely understood. Endothelial cells (ECs) and smooth muscle cells (SMCs) play crucial roles in a variety of cardiovascular functions, many of which are regulated via P2 receptors. However, their function in ECs and SMCs under microgravity condition is still unknown. In this study, ECs and SMCs were isolated from bovine aorta and differentiated from human mesenchymal stem cells (hMSCs), respectively. Subsequently, the cells were verified based on specific markers. An altered P2 receptor expression pattern was detected during the commitment of hMSC towards ECs and SMCs. The administration of natural and artificial P2 receptor agonists and antagonists directly affected the differentiation process. By using EC growth medium as conditioned medium, a vessel cell model was created to culture SMCs and vice versa. Within this study, we were able to show for the first time that the expression of some P2 receptors were altered in ECs and SMCs grown for 24h under simulated microgravity conditions. On the other hand, in some P2 receptor expressions such as P2X7 conditioned medium compensated this change.
In conclusion, our data show that P2 receptors play an important functional role in hMSC differentiation towards ECs and SMCs. Since some P2 receptor artificial ligands are already used as drugs for patients with cardiovascular diseases, it is reasonable to assume that in the future they might be promising candidates for treating cardiovascular deconditioning.
Chemie kann im Studium ganz schön kompliziert sein, besonders wenn es etwas mehr in die Tiefe geht. Dass man aber auch komplizierte Dinge leicht verständlich und bisweilen amüsant erklären kann, beweist dieses Lehrbuch. Stefanie Ortanderl und Ulf Ritgen erklären die Grundlagen der Chemie und so erfahren Sie, was Sie über Atommodelle, Bindungstypen und das Periodensystem wissen sollten.
Nitrile-type inhibitors are known to interact with cysteine proteases in a covalent-reversible manner. The chemotype of 3-cyano-3-aza-β-amino acid derivatives was designed in which the N-cyano group is centrally arranged in the molecule to allow for interactions with the nonprimed and primed binding regions of the target enzymes. These compounds were evaluated as inhibitors of the human cysteine cathepsins K, S, B, and L. They exhibited slow-binding behavior and were found to be exceptionally potent, in particular toward cathepsin K, with second-order rate constants up to 52 900 × 103 M–1 s–1.
Kriminalistik
(2014)