Abstract
Curcumin is a molecule found in turmeric root that has anti-inflammatory, antioxidant, and anti-tumor properties and has been widely used as both an herbal drug and a food additive to treat or prevent neurodegenerative diseases. To explore whether curcumin is able to ameliorate HIV-1-associated neurotoxicity, we treated a murine microglial cell line (N9) and primary rat cortical neurons with curcumin in the presence or absence of neurotoxic HIV-1 gp120 (V3 loop) protein. We found that HIV-1 gp120 profoundly induced N9 cells to produce reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1). HIV-1 gp120 also induced apoptosis of primary rat cortical neurons. Curcumin exerted a powerful inhibitory effect against HIV-1 gp120-induced neuronal damage, reducing the production of ROS, TNF-α and MCP-1 by N9 cells and inhibiting apoptosis of primary rat cortical neurons. Curcumin may exert its biological activities through inhibition of the delayed rectification and transient outward potassium (K+) current, as curcumin effectively reduced HIV-1 gp120-mediated elevation of the delayed rectification and transient outward K+ channel current in neurons. We conclude that HIV-1 gp120 increases ROS, TNF-α and MCP-1 production in microglia, and induces cortical neuron apoptosis by affecting the delayed rectification and transient outward K+ channel current. Curcumin reduces production of ROS and inflammatory mediators in HIV-1-gp120-stimulated microglia, and protects cortical neurons against HIV-1-mediated apoptosis, most likely through inhibition of HIV-1 gp120-induced elevation of the delayed rectification and transient outward K+ current.
Highlights
The human immunodeficiency virus type 1 (HIV-1) pandemic has claimed over 20 million lives, with 38.6 million people worldwide currently infected (2009 acquired immunodeficiency syndrome (AIDS) Epidemic Update by UNAIDS/WHO, www.unaids.org), and will continue to contribute to human morbidity and mortality as there is no vaccine available
We used the MTT assay to study the effects of HIV-1 gp120 V3 loop and curcumin on microglial viability
We found that HIV-1 gp120 V3 loop reduced microglia viability in a dose-dependent manner
Summary
The human immunodeficiency virus type 1 (HIV-1) pandemic has claimed over 20 million lives, with 38.6 million people worldwide currently infected (2009 AIDS Epidemic Update by UNAIDS/WHO, www.unaids.org), and will continue to contribute to human morbidity and mortality as there is no vaccine available. Prior to antiretroviral therapy (ART), neurologic disorders were the first manifestation of symptomatic HIV-1 infection, affecting roughly 10% –20% of patients and up to 60% of patients in the advanced stages of acquired immunodeficiency syndrome (AIDS) [1]. Neuroinflammation and microglial overactivation are involved in the pathogenesis of HIV-1-associated neurologic disorders. Over-activated microglial cells cause overproduction of various proinflammatory cytokines including tumor necrosis factor-alpha (TNF-a), interleukin 1b (IL-1b) and chemokines, which are believed to contribute to HIV1-associated neurologic disorders [2]
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