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Accueil > Bibliographie > A novel paraptosis pathway involving LEI/L-DNaseII for EGF-induced cell (...)

A novel paraptosis pathway involving LEI/L-DNaseII for (...)

Apoptosis. 2006 Mar ;11(3):367-75
A novel paraptosis pathway involving LEI/L-DNaseII for EGF-induced cell death in somato-lactotrope pituitary cells.
Fombonne J, Padron L, Enjalbert A, Krantic S, Torriglia A.

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.

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