Logo image
Back
Gene delivery of antioxidant enzymes inhibits human immunodeficiency virus type 1 gp120-induced expression of caspases
Journal article   Open access   Peer reviewed

Gene delivery of antioxidant enzymes inhibits human immunodeficiency virus type 1 gp120-induced expression of caspases

J-P Louboutin, L Agrawal, B A S Reyes, E J van Bockstaele and D S Strayer
Neuroscience, v 214, pp 68-77
12 Jul 2012
DOI: https://doi.org/10.1016/j.neuroscience.2012.03.061
PMID: 22531373
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc4707961View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Animals Antioxidants - administration & dosage Caspase Inhibitors - administration & dosage Caspases - biosynthesis Caspases - metabolism Female Gene Expression Regulation, Enzymologic Gene Transfer Techniques Glutathione Peroxidase - administration & dosage Glutathione Peroxidase - genetics HIV Envelope Protein gp120 - administration & dosage HIV Envelope Protein gp120 - antagonists & inhibitors HIV Envelope Protein gp120 - genetics Rats Rats, Sprague-Dawley Superoxide Dismutase - administration & dosage Superoxide Dismutase - genetics Superoxide Dismutase-1
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.

Metrics

6 Record Views
11 citations in Web of Science
13 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Web of Science research areas
Neurosciences
Logo image