Tobacco smoke induces mitochondrial depolarization along with cell death: effects of antioxidants.
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 (deltapsim), 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 deltapsim 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 deltapsim disruption and apoptosis, while the caspase inhibitor Z-VAD.Fmk did not affect deltapsim, though preventing apoptosis, and superoxide dismutase had no effect. Our data designate mitochondria as a target for ROS-mediated effects of tobacco smoke exposure.
Banzet
N
N
Laboratory of Respiratory Physiology, UFR Cochin Port-Royal, Paris, France.
François
D
D
Polla
B S
BS
D000111:Acetylcysteine / Q000494:pharmacology; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D009000:Monocytes / Q000187:drug effects* / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure*; D013482:Superoxide Dismutase / Q000494:pharmacology; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D000590:Amino Acid Chloromethyl Ketones; D000975:Antioxidants; D015853:Cysteine Proteinase Inhibitors; D016166:Free Radical Scavengers; D014028:Tobacco Smoke Pollution; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D013482:Superoxide Dismutase; D000111:Acetylcysteine