Rho-kinase inhibitor Y-27632 attenuates arsenic trioxide toxicity in H9c2 cardiomyoblastoma cells.

The purpose of this study is to examine the molecular mechanism underlying the toxicity of arsenic trioxide (ATO) in cardiac cells. H9c2 rat cardiomyoblastoma cells undergo apoptosis during exposure to the concentrations of ATO > 10 µM for 24 h. The process is accompanied by the activation of caspases and is suppressed by the pan-caspase inhibitor z-VAD. Since ATO-induced H9c2 cell death is suppressed by Rho-kinase (ROCK) inhibitor Y-27632, but not by any antioxidants tested, apoptosis by ATO seems to be initiated through a ROCK-dependent and reactive oxygen species-independent mechanism. During the execution of apoptosis by ATO, the induction of autophagy is also observed. Importantly, autophagy is accelerated in cells treated with ATO plus Y-27632, although Y-27632 alone does not induce autophagy. The cytoprotective effect of Y-27632 against ATO toxicity is abrogated by the co-administration of an autophagy inhibitor, 3-methyladenine, suggesting that autophagy contributes to the cytoprotection by Y-27632. Taken together, the data indicate that the activation of ROCK is required for apoptotic H9c2 cardiomyoblastoma cell death by ATO, and that the ROCK inhibition not only inhibits caspase-dependent apoptotic machinery, but also causes a rise in the cytoprotective autophagy processes during ATO exposure.

A case in which a bone fragment caused by a bullet made a second channel in addition to the bullet channel.

A 64-year-old male was found dead in his house with his face covered with blood and a 38-caliber revolver between his legs. He had been suffering from type 2 diabetes mellitus and aftereffects of cerebral infarction. Autopsy revealed a normal round contact wound in the left lateral cervical region. A bullet from the firearm had entered through the left lateral cervical region and traveled to the outer right sternocleidomastoid muscle. This also triggered another wound from the fifth cervical vertebra to the muscle tissue near the right cartilage thyroid. At the end of this channel, there were three bone fragments. Here, we report this interesting case with two channels caused by a bullet and by a resulting bone fragment. We also discuss the characteristics of an ear lobe injury found on the victim and show how this injury and blood and skin on the revolver were used as clues to determine the posture at the time of the shot.