Gene delivery of antioxidant enzymes inhibits human immunodeficiency virus type 1 gp120-induced expression of caspases.
Gene delivery of antioxidant enzymes inhibits human immunodeficiency virus type 1 gp120-induced expression of caspases.
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DOI：
10.1016/j.neuroscience.2012.03.061
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发表时间：
2012-07-12
期刊：
影响因子：
3.3
通讯作者：
Strayer DS
中科院分区：
文献类型：
--
作者：
Louboutin JP;Agrawal L;Reyes BA;van Bockstaele EJ;Strayer DS
Caspases are implicated in neuronal death in neurodegenerative and other Central Nervous System (CNS) diseases. In a rat model of HIV-1 associated neurocognitive disorders (HAND), we previously characterized HIV-1 envelope gp120-induced neuronal apoptosis by 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.
