Pathophysiologically relevant sources of oxidant and free radical species capable of PARP activation
| Reactive Oxygen or Nitrogen Species | Cellular Sources | Diffusible? | Relationship to PARP Activation |
|---|---|---|---|
| Superoxide anion | Mitochondrial respiratory chain, activated neutrophils, macrophages, xanthine oxidase, lipid peroxidation, catechol auto-oxidation, redox cycling | Yes | Does not induce DNA single strand breakage of PARP activation; although not a particularly potent oxidant, it can be cytotoxic via a number of PARP-independent mechanisms. |
| Hydrogen peroxide | Xanthine oxidase, mitochondrial respiratory chain, catechol auto-oxidation, redox cycling | Yes | Potent trigger of DNA single strand breakage and PARP activation via the generation of hydroxyl radical in the vicinity of DNA; potent oxidizing agent; can also be cytotoxic via a number of PARP-independent mechanisms. |
| Hydroxyl radical | From hydrogen peroxide, via the classic Fenton reaction. Monoamine oxidase in response to ionizing radiation, catechol auto-oxidation, redox cycling | No | Potent trigger of DNA single strand breakage and PARP activation; can also be cytotoxic via a number of PARP-independent mechanisms. The decomposition of peroxynitrite yields a hydroxyl radical-like intermediate, which, however, does not appear to be “free” hydroxyl radical. |
| Hypochlorous acid | Activated granulocytes | Yes | Does not induce DNA single strand breakage or PARP activation; can be cytotoxic via a number of PARP-independent mechanisms. At high concentrations, it is able to directly inactivate PARP. |
| Nitric oxide | Nitric-oxide synthases, acidification of nitrite, non-enzymatic pathways | Yes | Does not induce DNA single strand breakage or PARP activation, unless it combines with superoxide to produce peroxynitrite. Although not a particularly potent oxidant, can be cytotoxic via a number of PARP-independent mechanisms. It can also exert marked antioxidant and cytoprotective actions. |
| Peroxynitrite | Reaction of nitric oxide and superoxide. Nitric-oxide synthases can produce peroxynitrite under conditions of low cellular l-arginine levels | Yes | Potent trigger of DNA single strand breakage through a hydroxyl radical-like intermediate. Potent trigger of PARP-activation; can also be cytotoxic via a number of PARP-independent mechanisms. |
| Nitroxonium anion | Nitric oxide | Yes | Trigger of DNA single and double strand breakage; triggers PARP activation and associated cell death; can also be cytotoxic via a number of PARP-independent mechanisms. |