Ubiquitin-mediated stress response in the spinal cord after transient ischemia.
OBJECTIVE
Vulnerability of motor neurons in the spinal cord against ischemia is considered to play an important role in the development of delayed paraplegia after surgery of the thoracic aorta. However, the reasons for such vulnerability are not fully understood. Recently, the 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 the ubiquitin system after transient ischemia in the spinal cord.


METHODS
Fifteen minutes of spinal cord ischemia in rabbits was applied with the use of a balloon catheter. In this model, the spinal motor neuron shows selectively delayed neuronal death, whereas other spinal neurons such as interneurons survive. Immunohistochemical analysis and Western blotting for ubiquitin system molecules, ubiquitin, deubiquitylating enzyme (ubiquitin carboxy-terminal hydrolase 1), and ubiquitin-ligase parkin were examined.


RESULTS
In cytoplasm, ubiquitin and ubiquitin carboxy-terminal hydrolase 1 were strongly induced both in interneuron and motor neuron at the early stage of reperfusion, but the sustained expression was observed only in motor neuron. Parkin was induced strongly at 3 hours after the reperfusion, but the immunoreactivity returned to the sham control level at 6 hours in both neurons. In the nuclei, ubiquitin, ubiquitin carboxy-terminal hydrolase 1, and parkin were strongly induced in interneuron, whereas no upregulation of these proteins was observed in motor neuron.


CONCLUSIONS
These results indicate that the vulnerability of motor neuron of the spinal cord might be partially attributed to the different response in ubiquitin-mediated stress response after transient ischemia.
Yamauchi
Takashi
T
Department of Cardiovascular Surgery, Osaka University Graduate school of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. yamataka@surg1.med.osaka-u.ac.jp
Sakurai
Masahiro
M
Abe
Koji
K
Matsumiya
Goro
G
Sawa
Yoshiki
Y
D000818:Animals; D004195:Disease Models, Animal; D007395:Interneurons / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011817:Rabbits; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020760:Spinal Cord Ischemia / Q000378:metabolism* / Q000503:physiopathology; D025801:Ubiquitin / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase; D046988:Proteasome Endopeptidase Complex