Manganese superoxide dismutase induced by TNF-α is regulated transcriptionally by NF-κB after spinal cord injury in rats

Tae Y. Yune, Sang M. Lee, Sun J. Kim, Hong K. Park, Young J. Oh, Young C. Kim, George J. Markelonis, Tae H. Oh

Research output: Contribution to journalArticle

31 Citations (Scopus)

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-α administered 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-α into 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-α may be an inducer of NF-ΚB activation and MnSOD expression after SCI and that MnSOD expression induced by TNF-α is likely mediated through activation of NF-ΚB.

Original languageEnglish
Pages (from-to)1778-1794
Number of pages17
JournalJournal of Neurotrauma
Volume21
Issue number12
DOIs
Publication statusPublished - 2004 Dec 1

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

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