Epidermal growth factor triggers an original, caspase-independent pituitary cell death with heterogeneous phenotype

Autor: Olivier Bosler, Alain Enjalbert, Emmanuelle Danty, Joanna Fombonne, Ramahefarizo Rasolonjanahary, Sylvie Thirion, Slavica Krantic, Patrick Mehlen, Stéphanie Reix, Geneviéve Laforge-Anglade
Přispěvatelé: Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2004
Předmět:
Cytoplasm
Time Factors
Cell division
[SDV]Life Sciences [q-bio]
Apoptosis
Cell Separation
Mitochondrion
western immunoblotting
séparation cellulaire
0302 clinical medicine
Epidermal growth factor
rat
Caspase
0303 health sciences
Microscopy
Confocal
biology
Cell Death
Cytochromes c
Articles
Flow Cytometry
Immunohistochemistry
Chromatin
Cell biology
Mitochondria
Phenotype
Proto-Oncogene Proteins c-bcl-2
Caspases
Pituitary Gland
protéine des proto oncogènes
Programmed cell death
Blotting
Western
cytométrie de flux
DNA Fragmentation
Transfection
technique immunoblotting
Cell Line
03 medical and health sciences
Microscopy
Electron
Transmission
otorhinolaryngologic diseases
Animals
fragmentation de l'adn
Molecular Biology
030304 developmental biology
apoptose
Epidermal Growth Factor
Autophagy
Cell Biology
Rats
hypophyse
biology.protein
chromatine
030217 neurology & neurosurgery
Zdroj: Molecular Biology of the Cell
Molecular Biology of the Cell, American Society for Cell Biology, 2004, 15 (11), pp.4938-4948. ⟨10.1091/mbc.E04-07-0601⟩
ISSN: 1059-1524
1939-4586
DOI: 10.1091/mbc.E04-07-0601⟩
Popis: Programmed cell death (PCD) is physiologically involved in the regulation of cell division and differentiation. It encompasses caspase-dependent mitochondrial and nonmitochondrial pathways. Additional caspase-independent pathways have been characterized in mitochondrial PCDs but remain hypothetical in nonmitochondrial PCDs. Epidermal growth factor (EGF) has been shown to inhibit division of pituitary somato-lactotrope cells occurring in parallel with EGF-mediated differentiation of these precursors into lactotrope cells. We show here that in somato-lactotrope pituitary cell line GH4C1, EGF triggers a PCD characterized by an apoptosis-like DNA fragmentation, insensitivity to broad-range caspase inhibitors, and absence of either cytochrome c or apoptosis-inducing factor release from mitochondria. Dying cells display loose chromatin clustering and numerous cytoplasmic vacuoles, a fraction of which are autophagic, thus conferring a heterogeneous phenotype to this PCD. Moreover, overexpression of cell death inhibitor Bcl-2 prevented not only the EGF-induced PCD but also its prodifferentiation effects, thus pointing to a mechanistic relationship existing between these two phenomena. Overall, the characterized differentiation-linked cell death represents an original form of caspase-independent PCD. The mechanisms underlying this PCD involve combinatorial engagement of discrete death effectors leading to a heterogeneous death phenotype that might be evolutionary related to PCD seen during the differentiation of some unicellular organisms.
Databáze: OpenAIRE
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