Cell death takes two distinct forms, necrosis and apoptosis. Necrosis is a degenerative process that follows irreversible injury to the cell. Apoptosis, a Greek word that refers to the dropping of leaves from the tree, is an active process requiring protein synthesis for its execution and might perform either a homeostatic or a pathological role. As a simple distinction, apoptosis requires activation of cell signaling whereas necrosis does not. Apoptosis produces characteristic morphological changes including shrinkage of the cell, cytoplasmic blebbing, rounding of the cell (loss of adhesion or anoikis), condensation of the nuclear chromatin and cytoplasm, fragmentation of the nucleus, and budding of the whole cell to produce membrane-bounded bodies in which organelles are initially intact (1-3). These bodies are phagocytosed and digested by adjacent cells without evidence of inflammation. An important and overlooked characteristic is the presence of cell shrinkage, hence the original term of shrinking necrosis (1,2). Other distinguishing features between apoptosis and necrosis include rupture of lysosomes and the internucleosome cleavage of DNA observed in apoptosis that does not resemble the random DNA degradation observed in necrosis (4).
Despite the morphological and biochemical distinctions, it is important to realize that under pathological conditions both apoptosis and necrosis might result from the same process and that the difference in pathology might represent the degree of response to the same stimulus. For example, intracellular adenosine triphosphate (ATP) concentration might be critical in selection of the cell death pathway. A high ATP concentration favors apoptosis, whereas a low concentration promotes necrosis (5-8). The activity of poly(ADP-ribose) polymerase (PARP)-1 might be the pivotal point in this cell death decision, and as in other pathological conditions is important in the pathogenesis of diabetic complications (9-11). Although, poly ADP-ribosylation contributes to DNA repair and helps to maintain the genome, under conditions of oxidative stress there is overactivation of PARP that in turn consumes NAD(+), depletes ATP, and culminates in cell necrosis. If the ATP remains relatively high then PCD will occur by activation of caspases.
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