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• W1973882307 abstract "HIV-associated dementia, like several other neurodegenerative diseases, is characterized by selective degeneration of neurons amidst survival of glial cells like astroglia. The molecular basis of such selective susceptibility within the same milieu remains largely unknown. Neurons are rarely infected by the virus. However, they are vulnerable to viral products, like HIV-1 coat protein gp120. Interestingly, gp120 induced oxidative stress in neurons, but not in astroglia. This led us to postulate that astroglia were armed with a more efficient antioxidant system than neurons. Here, we report that the constitutive level of MnSOD (SOD2), the major cellular antioxidant enzyme, is significantly higher in astroglia than in neurons. Furthermore, gp120 treatment enhanced MnSOD levels in astroglia but decreased the same in neurons. This increase in astroglial MnSOD was dependent on NF-κB, the crucial transcription factor required for sod2 gene transcription. Blocking NF-κB with p65-antisense, p65-si-RNA, or a specific inhibitor, NBD peptide, led to reduced MnSOD levels and enhanced vulnerability of astroglia to gp120. Additionally, neurons were found to have a lower constitutive level of NF-κB p65 than astrocytes. Overexpression of p65 increased the level of MnSOD in neurons. This, in turn, elicited greater neuronal resistance to gp120. Taken together, our study suggests that astroglia manifest a higher threshold for gp120-induced lethality than neurons due to greater MnSOD availability, which is demonstrated due to greater level of NF-κB p65." @default.
• W1973882307 created "2016-06-24" @default.
• W1973882307 creator A5072870918 @default.
• W1973882307 creator A5087133073 @default.
• W1973882307 date "2007-06-15" @default.
• W1973882307 modified "2023-10-15" @default.
• W1973882307 title "Differential regulation of Mn-superoxide dismutase in neurons and astroglia by HIV-1 gp120: Implications for HIV-associated dementia" @default.
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• W1973882307 doi "https://doi.org/10.1016/j.freeradbiomed.2007.03.022" @default.
• W1973882307 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1955471" @default.
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