The role of nitric oxide in cell injury.

Nitric oxide (NO) is a pathophysiological mediator with unique signal transducing properties. Signaling mechanisms are categorized as cGMP-dependent or cGMP-independent. Multiple interactions of NO with oxygen, superoxide, and transition metals determine the biological activity. Cyclic GMP-independent responses of NO account for the antimicrobial, the cytostatic, and the cytotoxic capacity of NO. Cytotoxicity is not only directed to harmful cells but also affects the NO-producing cell in a self-destructing loop. For macrophages and pancreatic beta-cells (RINm5F), we established NO-mediated apoptotic cell death. Endogenously generated or exogenously applied NO causes DNA cleavage after endonuclease activation. NO-mediated accumulation of the tumor suppressor p53 precedes apoptotic cell death.