Tobacco smoke induces both apoptosis and necrosis in mammalian cells: differential effects of HSP70.
Tobacco smoke (TS) has been implicated as a major risk factor in human pulmonary diseases including cancer. In this study, we used TS as a model of oxidative stress. TS-mediated oxidative stress has been shown to induce protein oxidation, DNA damage, and cell death. Here we investigated, in human and rodent cell lines, whether TS induces cell death by apoptosis or by necrosis. As described for classic oxidants, TS induced apoptosis at low concentrations and necrosis at higher concentrations. We have previously described the induction of heat shock (HS) protein (HSP) (in particular, HSP70) in human monocytes exposed to TS. HSP70 is implicated in the regulation of cell injury and cell death and, in particular, modulates apoptosis, as does the antiapoptotic oncoprotein Bcl-2. At both apoptotic and necrotic concentrations, TS induced a dose-dependent HSP70 expression, whereas Bcl-2 was induced only at necrotic concentrations. TS- or HS-induced HSP had no protective effects either on apoptosis or on necrosis, but HSP70 overexpression prevented TS-induced necrosis and consequently led to increased apoptosis. These results might reconcile the apparently contradictory data previously reported on the effects of HSP on apoptosis.
Laboratoire de Physiologie Respiratoire, Unité de Formation et de Recherche Cochin Port-Royal, 75014 Paris, France.
M
M
Vayssier
N
N
Banzet
D
D
François
K
K
Bellmann
B S
BS
Polla
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002466:Cell Nucleolus / Q000648:ultrastructure; D002467:Cell Nucleus / Q000648:ultrastructure*; D002843:Chromatin / Q000648:ultrastructure; D022041:Euchromatin; D019254:Genes, bcl-2; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006570:Heterochromatin / Q000648:ultrastructure; D006801:Humans; D007700:Kinetics; D008854:Microscopy, Electron; D008928:Mitochondria / Q000648:ultrastructure; D009336:Necrosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000473:pathology / Q000503:physiopathology*; D020298:U937 Cells
D002843:Chromatin; D022041:Euchromatin; D018840:HSP70 Heat-Shock Proteins; D006570:Heterochromatin; D019253:Proto-Oncogene Proteins c-bcl-2; D012906:Smoke