Induction of ubiquitin, UCH-L1 and parkin and selective vulnerability of motor neuron in spinal cord after transient ischemia

Background and aims: Vulnerability of motor neuron in spinal cord against ischemia is considered to play in the development of delayed paraplegia after operation of thoracic aorta. However, the reasons of such vulnerability are not fully understood. Recently, ubiquitin system has been reported to participate in neuronal cell death. In the present study, we investigated the expression of ubiquitin system molecules and discussed the relationship between the vulnerability and ubiquitin system after transient ischemia in spinal cord. Methods: Fifteen minutes spinal cord ischemia of rabbits was applied with use of a balloon catheter. In this model, spinal motor neuron shows selectively delayed neuronal death whereas other spinal neuron such as inter neurons survive. Immunohistochemical analysis and western blotting for ubiquitin system molecules, ubiquitin, deubiquitylating enzyme ubiquitin (carboxy-terminal hydrolase 1;UCH-L1) and E3 ubiquitin ligase parkin, were examined. Results: In cytoplasm, ubiquitin and UCH-LI were induced strongly both in inter neuron and motor neuron at early stage of reperfusion, but the prolonged expression was observed in motor neuron. Parkin was induced strongly at 3 hr after reperfusion, but the immunoreactivity returned to almost the same level of sham group at 6 hr in both neurons. In neuclei, ubiquitin, UCH-L1 and parkin were strongly induced in inter neuron whereas no upregulation of these proteins were observed in motor neuron. Conclusions: These results indicate that the vulnerability of motor neuron of spinal cord might be partially attributed to the different response in ubiquitin and its related molecule response after transient ischemia.