[HTML][HTML] Poly (ADP-ribose) polymerase-1-mediated cell death in astrocytes requires NAD+ depletion and mitochondrial permeability transition

CC Alano, W Ying, RA Swanson - Journal of Biological Chemistry, 2004 - ASBMB
Extensive activation of poly (ADP-ribose) polymerase-1 (PARP-1) by DNA damage is a
major cause of caspase-independent cell death in ischemia and inflammation. Here we
show that NAD+ depletion and mitochondrial permeability transition (MPT) are sequential
and necessary steps in PARP-1-mediated cell death. Cultured mouse astrocytes were
treated with the cytotoxic concentrations of N-methyl-N′-nitro-N-nitrosoguanidine or 3-
morpholinosydnonimine to induce DNA damage and PARP-1 activation. The resulting cell …