Nicotine induces oxidative stress and activates nuclear transcription factor kappa B in rat mesencephalic cells

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 H₂O₂ can act as signal transducing agents. Nuclear transcription factor κB (NF-κB) 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-κB by binding to consensus sequence of DNA. Nicotine added to cell culture stimulates the degradation of IκB-α subunit in 2 h. Further activation of c-Jun terminal kinase indicates that nicotine induces oxidative stress leading to activation of stress dependent NF-κB pathway in mesencephalic cells.