Tobacco smoke induces mitochondrial depolarization along with cell death: Effects of antioxidants

Abstract

Smoking has been associated with a large number of diseases, in particular cancers. Among the many substances identified in tobacco smoke, reactive oxygen species (ROS) are major carcinogens. We have previously reported that exposure of mammalian cells to tobacco smoke induces the expression of stress proteins, as well as apoptosis (programmed cell death). Here we examined the effects of tobacco smoke on mitochondrial membrane potential (Δψm), since mitochondria have been proposed to control the effector phase of apoptosis. We used normal human monocytes for these experiments, with the prospect for application of Δψm as a biomarker of oxidative stress. Tobacco smoke induced mitochondrial depolarization at 3 h, and apoptosis (or necrosis for higher concentrations) after 16 h. Apoptosis was assessed by both a functional approach (annexin V binding) and morphological analysis (electron microscopy). N-acetyl-cysteine prevented tobacco smoke-induced Δψm disruption and apoptosis, while the caspase inhibitor Z-VAD.Fmk did not affect Δψm, though preventing apoptosis, and superoxide dismutase had no effect. Our data designate mitochondria as a target for ROS-mediated effects of tobacco smoke exposure.