A novel paraptosis pathway involving LEI/L-DNaseII for EGF-induced cell death in somato-lactotrope pituitary cells |
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Authors: | J Fombonne L Padrón A Enjalbert S Krantic A Torriglia |
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Institution: | (1) Interactions Cellulaires Neuroendocriniennes (ICNE), Unité Mixte de Recherche (UMR6544) Centre National de Recherche Scientifique (CNRS)/Université de la Méditerranée, Institut Jean Roche, Faculté de Médecine Nord 13916, Marseille, France;(2) INSERM U598, 15, rue de l’école de Médecine, 75006 Paris;(3) Institut de Neurobiologie de la Méditerranée (INMED), INSERM U29, Parc Scientifique de Luminy, Cedex 09, France;(4) Institut de Neurobiologie de la Méditerranée (INMED), INSERM U29, Parc Scientifique de Luminy—BP13, 13 273 Marseille, Cedex 09, France |
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Abstract: | We have recently reported that EGF triggers an original form of cell death in pituitary cell line (GH4C1) with a phenotype
sharing some characteristics of both apoptosis (internucleosomal DNA fragmentation) and paraptosis (caspase-independence and
cytoplasmic vacuolization). However, the endonuclease involved in EGF-induced DNA fragmentation has not been assessed so far.
In the present work we therefore further explored the putative paraptosis involvement in EGF-induced cell death and asked
whether L-DNaseII might be involved. Indeed, this endonuclease is known to mediate internucleosomal DNA fragmentation in caspase
independent manner. Our Western blot, immunocytochemistry and enzymatic measurement assays show that EGF triggers a cleavage
of Leukocyte Elastase Inhibitor (LEI) precursor into L-DNaseII, its subsequent enzymatic activation and nuclear translocation
thus pointing to the involvement of this endonuclease pathway in caspase-independent DNA fragmentation. In addition, EGF-induced
cell death can be blocked by paraptosis inhibitor AIP-1/Alix, but not with its anti-apoptotic C-terminal fragment (Alix-CT).
Altogether these data suggest that EGF-induced cell death defines a novel, L-DNaseII-mediated form of paraptosis.
This work was supported by fellowships from Fondation pour la Recherche medicale (FRM: FDT20030627283), from Association pour
la Recherche contre le Cancer (ARC: ML/MLD/CM-A04/4) to JF and Retina France to AT and LP.
These two authors equally contributed to this work. |
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Keywords: | AIP-1/Alix caspase-independent pathway L-DNaseII paraptosis |
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