title: Gene delivery of antioxidant enzymes inhibits human immunodeficiency virus type 1 gp120-induced expression of caspases.
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.
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, United States. jplouboutin@hotmail.com
authors.forename: J-P
authors.initials: JP
authors.lastname: Louboutin
authors.forename: L
authors.initials: L
authors.lastname: Agrawal
authors.forename: B A S
authors.initials: BA
authors.lastname: Reyes
authors.forename: E J
authors.initials: EJ
authors.lastname: van Bockstaele
authors.forename: D S
authors.initials: DS
authors.lastname: Strayer
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D061945:Caspase Inhibitors / Q000008:administration & dosage*; D020169:Caspases / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D018014:Gene Transfer Techniques; D005979:Glutathione Peroxidase / Q000008:administration & dosage* / Q000235:genetics; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000008:administration & dosage* / Q000235:genetics; D000072105:Superoxide Dismutase-1; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000975:Antioxidants; D061945:Caspase Inhibitors; D015699:HIV Envelope Protein gp120; C000606290:SOD1 protein, human; C514793:gp120 protein, Human immunodeficiency virus 1; D005979:Glutathione Peroxidase; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D020169:Caspases; D000094765:Glutathione Peroxidase GPX1; C000722069:Gpx1 protein, rat