Curcumin enhances paraquat-induced apoptosis of N27 mesencephalic cells via the generation of reactive oxygen species

Neurotoxicology. 2009 Nov;30(6):1008-18. doi: 10.1016/j.neuro.2009.07.016. Epub 2009 Aug 4.

Abstract

Curcumin, the active compound of the rhizome of Curcuma longa has anti-inflammatory, antioxidant and antiproliferative activities. This agent has been shown to regulate numerous transcription factors, cytokines, protein kinases, adhesion molecules, redox status and enzymes that have been linked to inflammation. While curcumin has been identified as an activator of apoptosis in several cell lines, the mechanism by which it initiates apoptosis, however, remains poorly understood. We considered curcumin from the point of view of its ability to protect against oxidative stress, the latter being one factor strongly implicated in the development of Parkinson's disease. Although the etiology of Parkinson's disease remains unknown, epidemiological studies have linked exposure to pesticides such paraquat to an increased risk of developing the condition. Analysis of the neurotoxic properties of these pesticide compounds has been focused on their ability to induce oxidative stress in neural cells. Given curcumin's capacity to protect against oxidative stress, it has been considered as a potential therapeutic agent for neurodegenerative diseases such as Parkinson's disease that involve an oxidative stress component. In the present report we describe the effect of curcumin in paraquat-mediated apoptosis of N27 mesencepahlic cells. We show that subtoxic concentrations of curcumin sensitize N27 mesencephalic cells to paraquat-mediated apoptosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cell Line, Transformed
  • Curcumin / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Flow Cytometry / methods
  • Gene Expression Regulation / drug effects
  • Herbicides / pharmacology*
  • Hydrogen Peroxide / pharmacology
  • Mesencephalon / cytology
  • Neurons / drug effects
  • Nitric Oxide Synthase Type I / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Paraquat / pharmacology*
  • Rats
  • Reactive Oxygen Species / metabolism*
  • Tetrazolium Salts
  • Thiazoles
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism
  • Vitamin E / pharmacology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Herbicides
  • Reactive Oxygen Species
  • Tetrazolium Salts
  • Thiazoles
  • Vitamin E
  • 3-nitrotyrosine
  • Tyrosine
  • Hydrogen Peroxide
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II
  • Caspase 3
  • thiazolyl blue
  • Curcumin
  • Paraquat
  • Acetylcysteine