Journal
NEUROCHEMICAL RESEARCH
Volume 27, Issue 11, Pages 1535-1542Publisher
KLUWER ACADEMIC/PLENUM PUBL
DOI: 10.1023/A:1021608724117
Keywords
TNF; NF kappa B; MnSOD; ROS; microglia; oligodendrocytes
Categories
Funding
- NICHD NIH HHS [HD06576] Funding Source: Medline
Ask authors/readers for more resources
Tumor necrosis factor (TNF)-family cytokines induce reactive oxygen species (ROS) that injure vulnerable populations of brain cells. Among glia, oligodendrocytes are particularly susceptible to TNF-induced ROS whereas microglia are protected. We previously found that oligodendrocytes in vitro predominantly express the p55 type-1 TNF receptor, while microglial cells express both type-1 and p75 type-2 receptors. We hypothesized that differential TNF receptor expression and attendant signaling underlies the relative vulnerability of oligodendrocytes, versus microglia, to TNF-induced injury. To test this hypothesis, purified cultures of glial cells were incubated 0-48 hr with TNFalpha or lymphotoxin-alpha, following which levels of ROS, glutathione (GSH), nuclear factor kappa-B (NFkappaB) translocation, and anti-oxidant proteins and activity were measured. 48 hr exposure to TNF increased ROS levels 28% and decreased GSH levels 17% in oligodendrocytes, but decreased levels ROS levels 24% and increased GSH levels 112% increase in microglia. Thirty to 180 min exposure to TNF increased NFkappaB nuclear translocation to a greater extent and for a longer time in microglia versus oligodendrocytes, and this was followed 24-48 hr later with 3- to 13-fold increases in microglia manganese superoxide dismutase protein levels and 6-fold increases in enzyme activity. Collectively, these data suggest that signals transduced through the p75 receptor activate anti-oxidant mechanisms that protect microglia from TNF-induced injury. Lacking such signals, oligodendrocytes are considerably more vulnerable to the injurious effects of TNF.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available