Nicotine Induces Oxidative Stress and Activates Nuclear Transcription Factor Kappa B in Rat Mesencephalic Cells

Mol Cell Biochem. 2007 Mar;297(1-2):93-9. doi: 10.1007/s11010-006-9333-1. Epub 2006 Oct 5.

Abstract

Cigarette smoke is a complex mixture of more than 4700 chemical compounds including free radicals and oxidants. Toxicity exhibited by cigarette smoke may be due to combined action of these compounds inducing many cellular processes mediated through reactive oxygen species (ROS). Major player probably nicotine as it is present in tobacco, in higher concentrations. The compounds that induce intracellular oxidative stress recognized as the important agents involved in the damage of biological molecules. Experiments using animal and cell culture model systems suggested that moderately higher concentrations of some forms of ROS like NO and H(2)O(2) can act as signal transducing agents. Nuclear transcription factor kappaB (NF-kappaB) an inducible transcription factor detected in neurons found to be involved in many biological processes such as inflammation, innate immunity, development, apoptosis, and antiapoptosis. Our present study demonstrates that nicotine induces ROS levels in a dose dependent manner in rat mesencephalic cells. Electro mobility shift analysis showed that nicotine activates inducible NF-kappaB by binding to consensus sequence of DNA. Nicotine added to cell culture stimulates the degradation of IkappaB-alpha subunit in 2 h. Further activation of c-Jun terminal kinase indicates that nicotine induces oxidative stress leading to activation of stress dependent NF-kappaB pathway in mesencephalic cells.

Publication types

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

MeSH terms

  • Animals
  • Cell Line
  • DNA / metabolism
  • Enzyme Activation / drug effects
  • I-kappa B Proteins / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Mesencephalon / cytology*
  • Mesencephalon / drug effects*
  • Mesencephalon / metabolism
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism*
  • Nicotine / pharmacology*
  • Oxidative Stress / drug effects*
  • Protein Binding / drug effects
  • Protein Processing, Post-Translational / drug effects
  • Rats
  • Reactive Oxygen Species / metabolism
  • Time Factors

Substances

  • I-kappa B Proteins
  • NF-kappa B
  • Nfkbia protein, rat
  • Reactive Oxygen Species
  • NF-KappaB Inhibitor alpha
  • Nicotine
  • DNA
  • JNK Mitogen-Activated Protein Kinases