Effects of tobacco smoke and benzo[a]pyrene on human endothelial cell and monocyte stress responses.
Smoking is an important risk factor for atherosclerosis. We compared tobacco smoke filtrate with benzo[a]pyrene (a prominent xenobiotic component of tobacco smoke) for the capacity to induce stress proteins and cause cell death in human monocytes and vascular endothelial cells, two cell types that are involved in the formation of atherosclerotic lesions. Exposure to freshly prepared filtrates of tobacco smoke induced in both monocytes and endothelial cells expression of the inducible heat shock protein (HSP)70 and heme oxygenase-1 (HO-1) and produced loss of mitochondrial membrane potential. Later, cell death by apoptosis or necrosis occurred depending on the concentration of tobacco smoke. These toxic effects could be prevented by the antioxidant N-acetylcysteine. In contrast, exposure of these cells to benzo[a]pyrene alone evoked neither stress proteins nor mitochondrial damage but did induce cell death by necrosis. Thus our results indicate that tobacco smoke rapidly induces complex oxidant-mediated stress responses in both vascular endothelial cells and circulating monocytes that are independent of the benzo[a]pyrene content of the smoke.
Vayssier-Taussat
M
M
Laboratoire de Physiologie Respiratoire, Université Paris V, Faculté Cochin, 75014 Paris, France.
Camilli
T
T
Aron
Y
Y
Meplan
C
C
Hainaut
P
P
Polla
B S
BS
Weksler
B
B
D000111:Acetylcysteine / Q000494:pharmacology; D001161:Arteriosclerosis / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000009:adverse effects*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins; D008928:Mitochondria / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*
D016166:Free Radical Scavengers; D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; D001564:Benzo(a)pyrene; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D005978:Glutathione; D000111:Acetylcysteine