A selective plasmin inhibitor, trans-aminomethylcyclohexanecarbonyl-L-(O-picolyl)tyrosine-octylamide (YO-2), induces thymocyte apoptosis
Eibai Lee 1, Riyo Enomoto, Kazu Takemura, Yuko Tsuda, Yoshio Okada

Treating rat thymocytes with YO-2, a singular inhibitor of plasmin, led to a rise in DNA fragmentation. DNA fragmentation seemed to be caused by another YO compounds for example YO-, -3, -4 and -5. These YO compounds would be the inhibitor of plasmin activity. However, YO-1, -6 and -8 that hardly hinder plasmin activity didn’t have impact on DNA fragmentation. Analysis of fragmented DNA from thymocytes given YO-2 by agarose gel electrophoresis says the compound caused internucleosomal DNA fragmentation. Additionally, knowing from the laser checking microscopy, annexin V-positive and propidium iodide-negative cells were elevated by treating cells using the compound. Furthermore, chromatin condensation was noticed in thymocytes given the compound. These results shown that YO-2 induces thymocyte apoptosis. There appeared to become some correlation between your apoptosis caused by YO compounds as well as their plasmin inhibitory effect. However, since the other protease inhibitors including pepstatin A, leupeptin, AEBSF, DFP and E-64-d didn’t affect DNA fragmentation, YO compounds will probably have unique mechanism on plasmin in order to show the result alternatively plasmin-like proteases. The plasmin inhibitory activity might have a huge role in YO-2-caused apoptosis. In addition, the stimulations of caspase-8, -9 and -3-like activities were noticed in thymocytes given YO-2. These results claim that YO-2 induces thymocyte apoptosis via activation of caspase cascade.YO-01027