American Society of Hematology

ROS generation begins with the formation of O2−, which is produced by 1-electron reduction of molecular oxygen (O2). The first line of cellular defense against high O2− levels is dismutation of O2− into O2 and H2O2 by SOD. In the presence of nitric oxide (NO), O2− can more rapidly react with NO than with SOD to form ONOO−, a highly reactive ROS species. In lymphoma cells, downregulation of SOD1 expression increases intracellular ONOO− formation by reacting with NO, which is formed from arginine by NOSs. ONOO− can nitrate Y289 of B56 and leads to the dissociation of the PP2A-AC heterodimer from the Bcl-2–bound B56δ subunit of PP2A, resulting in the enhanced phosphorylation of Bcl-2 S70. This may confer resistance to drug-induced cell death. NOS, NO synthase.

ROS generation begins with the formation of O₂⁻, which is produced by 1-electron reduction of molecular oxygen (O₂). The first line of cellular defense against high O₂⁻ levels is dismutation of O₂⁻ into O₂ and H₂O₂ by SOD. In the presence of nitric oxide (NO), O₂⁻ can more rapidly react with NO than with SOD to form ONOO⁻, a highly reactive ROS species. In lymphoma cells, downregulation of SOD1 expression increases intracellular ONOO⁻ formation by reacting with NO, which is formed from arginine by NOSs. ONOO⁻ can nitrate Y289 of B56 and leads to the dissociation of the PP2A-AC heterodimer from the Bcl-2–bound B56δ subunit of PP2A, resulting in the enhanced phosphorylation of Bcl-2 S70. This may confer resistance to drug-induced cell death. NOS, NO synthase.

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