Curcumin protects microglia and primary rat cortical neurons against HIV-1 gp120-mediated inflammation and apoptosis

• Published in: PloS one Vol. 8; no. 8; p. e70565
• Main Authors: Guo, Luyan, Xing, Yanyan, Pan, Rui, Jiang, Mingliang, Gong, Zheng, Lin, Liqing, Wang, Junbing, Xiong, Guoyin, Dong, Jun
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.08.2013; Public Library of Science (PLoS)
• Subjects: Animals; Anti-inflammatory diet; Anticancer properties; Antioxidants; Apoptosis; Apoptosis - drug effects; Biology; Brain research; Cell Line; Cell Survival - drug effects; Cerebral Cortex - cytology; Chinese medicine; Curcumin; Curcumin - pharmacology; Cytoprotection - drug effects; Food additives; Glycoprotein gp120; HIV; HIV Envelope Protein gp120 - metabolism; Human immunodeficiency virus; Inflammation; Inflammation - metabolism; Inflammation - pathology; Inflammation - prevention & control; Inflammation Mediators - metabolism; Inhibition; Kinases; Medicine; Meetings; Mice; Microglia; Microglia - cytology; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Nervous system diseases; Neurodegenerative diseases; Neurological diseases; Neurons; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Neurons - virology; Neurotoxicity; Oxygen; Potassium; Potassium - metabolism; Potassium channels; Potassium Channels, Voltage-Gated - metabolism; Rats; Rats, Sprague-Dawley; Reactive oxygen species; Reactive Oxygen Species - metabolism; Tumor necrosis factor; Tumor necrosis factor-α; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0070565

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.