title: 4-Hydroxynonenal-induced cell death in murine alveolar macrophages.
abstract: Oxidative stress is known to cause apoptosis in many cell types, yet the mechanism of oxidative stress-induced apoptosis is not clear. Oxidative stress has been described to cause peroxidation of polyunsaturated fatty acids. 4-Hydroxynonenal (HNE) is a diffusible product of lipid peroxidation and has been shown to be toxic to cells. In this study, the effects of HNE on isolated alveolar macrophages (AM) from two murine strains (C3H/HeJ and C57BL/6J) were examined. HNE induced the formation of protein adducts in AMs from both strains of mice in a dose-dependent manner, and the amounts of HNE-protein adducts formed in cells from both strains were very similar. In the HNE dose range from 1 to 100 microM, AMs from both strains had very little necrosis as shown by trypan blue staining. However, AMs from both C3H/HeJ and C57BL/6J mice had extensive apoptosis at 100 microM HNE, but little or no apoptosis at 25 microM HNE. Furthermore, AMs from C57BL/6J mice had significant apoptosis at 50 microM HNE while AMs from C3H/HeJ mice had no significant apoptosis at this dose. At low doses of HNE (10 to 25 microM), there was induction of heme oxygenase 1. The data indicated that HNE induces apoptosis in murine macrophages, and cells from different strains of mice have different sensitivities to the HNE-induced apoptosis. The cause of the difference in susceptibility is not known, but it is possible that different stress response and/or apoptosis-regulating proteins may be in part responsible. Our observation that a product of lipid peroxidation causes apoptosis suggested that it might be a mediator for oxidative stress-induced apoptosis.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Texas Houston Health Science 77030, USA.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: R F
authors.initials: RF
authors.lastname: Hamilton
authors.forename: A
authors.initials: A
authors.lastname: Kirichenko
authors.forename: A
authors.initials: A
authors.lastname: Holian
mesh_terms: D000447:Aldehydes / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D004396:Coloring Agents / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000633:toxicity*; D004247:DNA / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D015227:Lipid Peroxidation / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009336:Necrosis / Q000139:chemically induced; D018384:Oxidative Stress / Q000187:drug effects; D011485:Protein Binding; D011506:Proteins / Q000032:analysis / Q000378:metabolism; D013045:Species Specificity; D014343:Trypan Blue / Q000737:chemistry
chemical_list: D000447:Aldehydes; D004396:Coloring Agents; D003432:Cross-Linking Reagents; D011506:Proteins; D004247:DNA; D014343:Trypan Blue; C027576:4-hydroxy-2-nonenal