Journal article
Gene delivery of antioxidant enzymes inhibits human immunodeficiency virus type 1 gp120-induced expression of caspases
Neuroscience, v 214, pp 68-77
12 Jul 2012
PMID: 22531373
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Caspases are implicated in neuronal death in neurodegenerative and other central nervous system (CNS) diseases. In a rat model of human immunodeficiency virus type 1 (HIV-1) associated neurocognitive disorders (HAND), we previously characterized HIV-1 envelope gp120-induced neuronal apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. In this model, neuronal apoptosis occurred probably via gp120-induced reactive oxygen species (ROS). Antioxidant gene delivery blunted gp120-related apoptosis. Here, we studied the effect of gp120 on different caspases (3, 6, 8, 9) expression. Caspases production increased in the rat caudate-putamen (CP) 6h after gp120 injection into the same structure. The expression of caspases peaked by 24h. Caspases colocalized mainly with neurons. Prior gene delivery of the antioxidant enzymes Cu/Zn superoxide dismutase (SOD1) or glutathione peroxidase (GPx1) into the CP before injecting gp120 there reduced levels of gp120-induced caspases, recapitulating the effect of antioxidant enzymes on gp120-induced apoptosis observed by TUNEL. Thus, HIV-1 gp120 increased caspases expression in the CP. Prior antioxidant enzyme treatment mitigated production of these caspases, probably by reducing ROS levels.
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Details
- Title
- Gene delivery of antioxidant enzymes inhibits human immunodeficiency virus type 1 gp120-induced expression of caspases
- Creators
- J-P Louboutin - Thomas Jefferson UniversityL Agrawal - Thomas Jefferson UniversityB A S Reyes - Thomas Jefferson UniversityE J van Bockstaele - Thomas Jefferson UniversityD S Strayer - Thomas Jefferson University
- Publication Details
- Neuroscience, v 214, pp 68-77
- Publisher
- Elsevier
- Grant note
- R21 MH069122 / NIMH NIH HHS K02 DA015395 / NIDA NIH HHS R01 MH070287 / NIMH NIH HHS MH70287 / NIMH NIH HHS MH69122 / NIMH NIH HHS AH48244 / BHP HRSA HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000305547500007
- Scopus ID
- 2-s2.0-84861829325
- Other Identifier
- 991021903405804721
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- Neurosciences