Parp and cell death or protection in rat primary astroglial cell cultures under LPS/IFNgamma induced proinflammatory conditions.
The enzyme poly(ADP-ribose)polymerase (PARP) has a leader role in the DNA damage survey mechanisms by its nick-sensor function, but it is also involved in the early events of the programmed cell death, particularly during inflammatory injury, as a coactivator of NF-kB. In the present study, we evaluated the PARP involvement in the mechanisms of protection and/or cell death in rat astroglial cell cultures during the early phase of proinflammatory commitment after lipopolysaccharide and interferon gamma treatment. According with the recent findings that PARP-1 phosphorylation by MAPK/ERK-2 pathway seems to modulate PARP activation, in time course experiments we demonstrated that a very early PARP activation and expression is able to trigger a cell death pathway, DNA damage independent, during strong proinflammatory insults, maintaining its role of guardian of the genome stability only during the normal cell cycling.
Spina-Purrello
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V
Department of Chemical Sciences, Section of Biochemistry and Molecular Biology, Medical Faculty, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.
Patti
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D
Giuffrida-Stella
A M
AM
Nicoletti
V G
VG