The double-edged role of nitric oxide in apoptosis signalling: focused on liver

Nitric oxide (NO) is a free radical endogenously produced by nitric oxide synthase. This molecule possesses many important functions in the mammalian organism. The role of NO in regulating cell death and proliferation is now widely recognized. In cultured primary hepatocytes both proapoptotic and antiapoptotic NO effects have been reported. However, most reports support its role in the inhibition of apoptosis. NO has been shown to suppress apoptosis in a model of inflammation and cholestasis, and inhibits spontaneous apoptosis. NO antiapoptotic function was exerted via inhibition of both activity and activation of caspases either directly by nitrosylation, or indirectly via an cGMP-dependent pathway. Both spontaneous and induced hepatocyte apoptosis can be determined by biochemical and morphological methods, which cover various aspects of the apoptotic process, and have a different specificity for detection of apoptotic cell death.