Research Article
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Published Online: 1 December 2004

Manganese Superoxide Dismutase Induced by TNF-β Is Regulated Transcriptionally by NF-κB after Spinal Cord Injury in Rats

Publication: Journal of Neurotrauma
Volume 21, Issue Number 12

Abstract

Antioxidant enzymes including superoxide dismutase (SOD) may play a role in the mechanism by which cells counteract the deleterious effects of reactive oxygen species (ROS) after spinal cord injury (SCI). Cu/Zn and MnSOD are especially potent scavengers of superoxide anion and likely serve important cytoprotective roles against cellular damage. We investigated expression of SOD after SCI to address its role during the early stages of injury. MnSOD activity was increased 4 h after SCI and persisted at elevated levels up to 24–48 h; by contrast, Cu/ZnSOD activity was not changed. RT-PCR and Western blot analyses showed increased levels of MnSOD mRNA and protein, respectively, by 4 h and reached maximum levels by 24–48 h. Double immunostaining revealed that MnSOD protein was localized within neurons and oligodendrocytes. Tumor necrosis factor–α(TNF-α) was administered locally into uninjured spinal cords to examine potential mechanisms for MnSOD induction after injury. TNF-αadministered exogenously increased MnSOD expression in uninjured spinal cords. Western blot and immunostaining also revealed that a transcription factor, NF-κB, was activated and translocated into the nuclei of neurons and oligodendrocytes. By contrast, administration of neutralizing antibody against TNF-αinto injured spinal cords attenuated the increase in MnSOD expression and activation of NF-κB. Double immunostaining revealed that MnSOD was co-localized with NF-κB in neurons and oligodendrocytes after SCI. These results suggest that TNF-αmay be an inducer of NF-κB activation and MnSOD expression after SCI and that MnSOD expression induced by TNF-αis likely mediated through activation of NF-κB.

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cover image Journal of Neurotrauma
Journal of Neurotrauma
Volume 21Issue Number 12December 2004
Pages: 1778 - 1794
PubMed: 15684769

History

Published in print: December 2004
Published online: 1 December 2004

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Tae Y. Yune
Biomedical Research Center, Korea Institute of Science & Technology, Seoul, Korea.
Sang M. Lee
Biomedical Research Center, Korea Institute of Science & Technology, Seoul, Korea.
Sun J. Kim
Biomedical Research Center, Korea Institute of Science & Technology, Seoul, Korea.
Hong K. Park
Biomedical Research Center, Korea Institute of Science & Technology, Seoul, Korea.
Young J. Oh
Department of Biology, Yonsei University College of Science, Seoul, Korea.
Young C. Kim
Seoul National University College of Pharmacy, Seoul, Korea.
George J. Markelonis
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland.
Tae H. Oh
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland.

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