3-Nitrofluoranthene (3-NF) but not 3-aminofluoranthene (3-AF) elicits apoptosis as well as programmed necrosis in Hepa1c1c7 cells

Autor: Dominique Lagadic-Gossmann, Nana Asare, Marit Låg, Jørn A. Holme, Mary Rissel, Per E. Schwarze
Přispěvatelé: Division of Environmental Medicine, Norwegian Institute of Public Health [Oslo] (NIPH), Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Détoxication et réparation tissulaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Aurora (Egide), Norwegian Research Council, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Rok vydání: 2009
Předmět:
Programmed cell death
MESH: Cell Line
Tumor
p38 mitogen-activated protein kinases
Necroptosis
Blotting
Western
Apoptosis
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Biology
Toxicology
Paraptosis
Mice
Necrosis
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Microscopy
Electron
Transmission
Cell Line
Tumor
MESH: Cell Proliferation
Autophagy
Animals
MESH: Autophagy
MESH: Blotting
Western
MESH: Fluorenes
Cytotoxic T cell
MESH: Animals
Propidium iodide
MESH: Mice
Cell Proliferation
030304 developmental biology
MESH: Necrosis
Fluorenes
0303 health sciences
MESH: Apoptosis
3-Nitrofluoranthene
MESH: Mitogen-Activated Protein Kinases
Cell biology
chemistry
[SDV.TOX]Life Sciences [q-bio]/Toxicology
030220 oncology & carcinogenesis
MESH: Microscopy
Electron
Transmission
Mitogen-Activated Protein Kinases
3-Aminofluoranthene
Cell signalling
Zdroj: Toxicology
Toxicology, Elsevier, 2009, 255 (3), pp.140-50. ⟨10.1016/j.tox.2008.10.021⟩
Toxicology, 2009, 255 (3), pp.140-50. ⟨10.1016/j.tox.2008.10.021⟩
ISSN: 0300-483X
DOI: 10.1016/j.tox.2008.10.021
Popis: International audience; In this study, we show that the environmental pollutant, 3-nitrofluoranthene (3-NF) but not its amine form, 3-aminofluoranthene (3-AF), induces apoptosis as well as regulated necrosis with necroptotic features in Hepa1c1c7 cells. Upon exposure to 3-NF, both typical apoptotic and necrotic cells were observed. A large number of the cells exhibited a characteristic partial nuclear chromatin condensation. Cycloheximide completely attenuated 3-NF-induced cell death. Activation of caspase-8, -9, and -3 were observed. Moreover, Z-VAD-FMK decreased the apoptotic cells, whereas the number of propidium iodide (PI)-positive cells with partial chromatin condensation was reduced by Nec-1, an inhibitor of receptor interacting protein (RIP-1). Cyp1a1, but not nitric oxide synthase (NOS), appears to be involved in activation of 3-NF to reactive metabolites. Increase in the number as well as size of lysosomes, myelinosomes, and activation of autophagy were also observed. 3-NF induced phosphorylation of ERK1/2, JNK and p38 MAPKs. Interestingly, while inhibitors of ERK1/2 and JNK reduced apoptotic as well as necrotic cell death, the p38 inhibitor, SB202190 reduced only the necrotic cell death. Taken together, 3-NF elicits both apoptosis and a caspase-independent programmed cell death (PCD) with autophagic characteristics. Conversely, with 3-AF, no apparent cytotoxic effects besides a reduction in cell proliferation was observed.
Databáze: OpenAIRE
Externí odkaz: