APOPTOSIS IN THE ABSENCE OF POLY-(ADP-RIBOSE) POLYMERASE

Cleavage of poly-(ADP-ribose) polymerase is a process occurring early during the execution phase of apoptosis. Although in many experimental systems PARP cleavage indicates a point of no return, the significanc e of this proteolytic step for apoptosis remains unclear. Here we comp are the susceptibility of cells from wild-type mice and PARP-/- mice t o several inducers of apoptosis. Neither the susceptibility of hepatoc ytes towards CD95 or TNF-mediated apoptosis nor the activation of PARP -cleaving caspases was modified in PARP-/- liver cells. Thymocytes wit h either genotype exhibited similar sensitivity to treatments with cer amide, dexamethasone, or etoposide. The sensitivity of primary neurons towards apoptosis induced by staurosporine, colchicine, potassium wit hdrawal, peroxynitrite, or the neurotoxin MPP+ was also unaltered. The se data suggest that neither activation nor cleavage of PARP has a cau sal role in apoptotic cell death of primary, non-transformed cells. (C ) 1997 Academic Press.