UC San Diego
Antioxidant sestrin-2 redistribution to neuronal soma in human immunodeficiency virus-associated neurocognitive disorders
- Author(s): Soontornniyomkij, V
- Soontornniyomkij, B
- Moore, DJ
- Gouaux, B
- Masliah, E
- Tung, S
- Vinters, HV
- Grant, I
- Achim, CL
- et al.
Published Web Locationhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573843/
Sestrin-2 is involved in p53-dependent antioxidant defenses and in the maintenance of metabolic homeostasis. We hypothesize that sestrin-2 expression is altered in the brains of subjects diagnosed with human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) due to neuronal oxidative stress. We studied sestrin-2 immunoreactivity in 42 isocortex sections from HIV-1-infected subjects compared to 18 age-matched non-HIV controls and 19 advanced Alzheimer's disease (AD) cases. With HIV infection, the sestrin-2 immunoreactivity pattern shifted from neuropil predominance (N) to neuropil and neuronal-soma co-dominance (NS) and neuronal-soma predominance (S; P<0.0001, Chi-square test for linear trend). Among HIV cases showing the NS or S pattern, HAND cases were preferentially associated with the S pattern (n010 of 20) compared to cognitively intact cases (n01 of 11; P00.047, Fisher's exact test). In AD brains, sestrin-2 immunoreactivity was mostly intense in the neuropil and co-localized with phospho-Tau immunoreactivity in a subset of neurofibrillary lesions. Phospho-Tau-immunoreactive neurofibrillary lesions were rare in HIV cases and their occurrence was not associated with HAND. Levels of isocortical 8-hydroxy-deoxyguanosine (marker of nucleic acid oxidation) immunoreactivity were not significantly altered in HAND cases compared to cognitively intact HIV cases. In conclusion, the sestrin-2 immunoreactivity redistribution to neuronal soma in HAND suggests unique involvement of sestrin-2 in the pathophysiology of HAND, which is different from the role of sestrin-2 in AD pathogenesis. Alternatively, the difference in sestrin-2 immunoreactivity distribution between HAND and AD may be related to different degrees of severity or stages of oxidative stress. © Springer Science+Business Media, LLC 2012.
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