Effects of Hypoxia on the Ubiquitin-proteasome System in Primary Cortical Neuronal Cell Cultures / 체질인류학회지

The ubiquitin-proteasome system is crucial in maintaining cellular growth and metabolism. Dysfunction of this system may contribute to neurodegenerative diseases, such as Parkinson's disease. But its effects on primary neurons are largely unknown. In the present study, we investigated the effects of proteasome inhibitor and hypoxia on primary neuronal cultures to determine whether proteasomal malfunction induces neuronal death. Neuronal apoptosis increased in primary cultured cortical neurons with treatment of proteasomal inhibitor in normoxic condition and in the presence or absence of proteasomal inhibitor in hypoxic condition. Also expression of PARP and activated caspase 3 increased. NF-kappaB, a key transcription factor in this system expression increased in hypoxic condition and proteasomal inhibition. Interestingly, hypoxic condition induced an expression and accumulation of alpha-synuclein in neuron, one of components of Lewy body in Parkinson's disease. Our findings determine that hypoxic condition may affect the ubiquitin-proteasome system. Furthermore, it suggests that hypoxic condition and proteasomal inhibitors are involved, at least in parts, in neurodegeneration of mouse model for Parkinson's disease.

Development of the Single Nodular VX-2 Carcinoma Model in Rabbit Liver: Tissue Chip Implantation under Ultrasonographic Guidance

PURPOSE: To implant tissue chips in New Zealand rabbits, and thus redurce the frequency with which scattered VX2 carcinoma nodules and early metastasis develop in these animals. MATERIALS AND METHODS: VX2-carcinoma tissue chips of two different sizes were implanted under ultrasonographic guidance. In each of 12 New Zealand rabbits (group 1), there 1-mm tissue chips were implanted in the liver using an 18-gauge needle, and in the same way, one 3-mm chip with an added gelfoam pellet was implanted in the proximal lumen of the liver of each of ten other New Zealand rabbits (group 2). Three weeks after implantation, the animals underwent dvalphase CT scanning and were sacrificed, and the Number and size of tumor nodules, and metastasis were evaluated either macro-or microscopically. RESULTS: In ten rabbits in group I, a total of 21 nodules (16 in the liver, 5 in the peritoneal wall) were observed, which in nine rabbits in group 2, a total of ten nodules-all in the liver-were present. CT scans depicted tumor nodules in 50% of group-I rabbits, and in 29% those in group 2. Mean tumor diameter was 12 +/-9 mm in group 1 and 6.4 +/-3 mm in group 2. Histologic examination indicated the presence of nodular VX2 carcinoma, with varying degrees of central necrosis, a feature more prominent in group 2. CONCLUSION: To provide a well-localized tumor nodule in rabbit liver, tissue chip implantation of VX2 carcinoma, especially with added gelfoam, is a good alternative to intraparenchymal injection of tumor suspension.