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Figure 1 Proposed role of poly(adenosine diphosphate-ribose) polymerase (PARP) in oxidant-induced cellular dysfunction and necrosis. Oxygen and nitrogen-derived radicals cause stand breaks in deoxyribonucleic acid (DNA), activating PARP. Activation of PARP initiates an energy-consuming cycle by transferring adenosine diphosphate-ribose units from nicotinamide adenine dinucleotide (NAD⁺) to nuclear proteins resulting in rapid depletion of the intracellular NAD⁺ and adenosine triphosphate (ATP) pools, slowing the rate of glycolysis and mitochondrial respiration, eventually leading to cellular dysfunction and death. ADPR = adenosine diphosphate-ribose; NADH = reduced nicotinamide adenine dinucleotide; ONOO– = peroxynitrite.