The intimate relation between nitric oxide and superoxide in apoptosis and cell survival

Intra- and intercellular communication in or between cells allows adaptation to changes in the environment. Formation of reactive oxygen (ROS) and nitrogen (RNS) species in response to external insults gained considerable attention in provoking cell demise along an apoptotic subroute of cell death, thus attributing radical formation to pathologies. In close association, stabilization of the tumor suppressor p53 and activation of caspases convey proapoptotic signaling. Complexity was added with the notion that ROS and RNS signals overlap and/or produce synergistic as well as antagonistic effects. With respect to nitric oxide (NO) signaling, it became clear that the molecule is endowed with pro- or antiapoptotic signaling capabilities, depending to some extend on the concentration and cellular context, i.e., ROS generation. Here, some established concepts are summarized that allow an explanation of p53 accumulation under the impact of NO and an understanding of NO-evoked cell protection at the level of caspase inhibition, cyclic GMP formation, or expression of antiapoptotic proteins. In addition, the overlapping sphere of ROS and RNS signaling is recapitulated to appreciate cell physiology/pathology with the notion that marginal changes in the flux rates of either NO or superoxide may shift vital signals used for communication and cell survival into areas of pathology in close association with apoptosis/necrosis.