Signal interactions between nitric oxide and reactive oxygen intermediatesin the plant hypersensitive disease resistance response

Nitric oxide (NO) and reactive oxygen intermediates (ROIs) play key roles i n the activation of disease resistance mechanisms both in animals and plant s. In animals NO cooperates with ROIs to kill tumor cells and for macrophag e killing of bacteria. Such cytotoxic events occur because unregulated NO l evels drive a diffusion-limited reaction with O-2(-) to generate peroxynitr ite (ONOO-), a mediator of cellular injury in many biological systems. Here we show that in soybean cells unregulated NO production at the onset of a pathogen-induced hypersensitive response (HR) is not sufficient to activate hypersensitive cell death. The HR is triggered only by balanced production of NO and ROIs. Moreover, hypersensitive cell death is activated after int eraction of NO not with O-2(-) but with H2O2 generated from O-2(-) by super oxide dismutase. Increasing the level of O-2(-) reduces NO-mediated toxicit y, and ONOO- is not a mediator of hypersensitive cell death. During the HR, superoxide dismutase accelerates O-2(-) dismutation to H2O2 to minimize th e loss of NO by reaction with O-2(-) and to trigger hypersensitive cell dea th through NO/H2O2 cooperation. However, O-2(-) rather than H2O2 is the pri mary ROI signal for pathogen induction of glutathione S-transferase, and th e rates of production and dismutation of O-2(-) generated during the oxidat ive burst play a crucial role in the modulation and integration of NO/H2O2 signaling in the HR. Thus although plants and animals use a similar reperto ire of signals in disease resistance, ROIs and NO are deployed in strikingl y different ways to trigger host cell death.