Nitric oxide (NO): an effector of apoptosis

It is appreciated that the production of nitric oxide (NO) from L-arginine metabolism is an essential determinate of the innate immune system, importa nt for nonspecific host defense, as well as tumor and pathogen killing. Cyt otoxicity as a result of a substantial NO-formation is established to initi ate apoptosis, characterized by upregulation of the tumor suppressor p53, c hanges in the expression of pro- and anti-apoptotic Bcl-2 family members, c ytochrome c relocation, activation of caspases, chromatin condensation, and DNA fragmentation. Proof for the involvement of NO was demonstrated by blo cking adverse effects by NO-synthase inhibition. However, NO-toxicity is no t a constant value and NO may achieve cell protection as well. In part this is understood by transcription and translation of protective proteins, suc h as cyclooxygenase-2, Alternatively, protection may result as a consequenc e of a diffusion controlled NO/O-2(-) - (superoxide) interaction that redir ects the apoptotic initiating activity of NO towards protection. NO is endo wed with the unique ability to initiate and to block apoptosis, depending o n multiple variables that exist to be elucidated. The crosstalk between cel l destructive and protective signaling pathways under the modulatory influe nce of NO will determine the impact of NO in apoptotic cell death and survi val.