Curcumin Protects Microglia and Primary Rat Cortical Neurons Against HIV-1 gp120-mediated Inflammation and Apoptosis

PLoS One. 2013 Aug 6;8(8):e70565. doi: 10.1371/journal.pone.0070565. Print 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cell Line
  • Cell Survival / drug effects
  • Cerebral Cortex / cytology*
  • Curcumin / pharmacology*
  • Cytoprotection / drug effects*
  • HIV Envelope Protein gp120 / metabolism*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / prevention & control
  • Inflammation Mediators / metabolism
  • Mice
  • Microglia / cytology*
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / virology
  • Potassium / metabolism
  • Potassium Channels, Voltage-Gated / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism

Substances

  • HIV Envelope Protein gp120
  • Inflammation Mediators
  • Potassium Channels, Voltage-Gated
  • Reactive Oxygen Species
  • gp120 protein, Human immunodeficiency virus 1
  • Curcumin
  • Potassium

Grant support

This work was supported by National Natural Science Foundation of China, number 81171134; National Basic Research Program of China C973 program, number 2011CB707500; Science and Technology Foundation of Guangzhou, number 2010Y1-C291; Science and Technology Foundation of Guangdong, number 2010B030700017; The Key laboratory’s Open Fund of Jinan University, number 2011ZD003. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.