ß-Galactosidase-activated nitroxyl (HNO) donors provide insights into redox cross-talk in senescent cells.

The cross-talk among reductive and oxidative species (redox cross-talk), especially those derived from sulfur, nitrogen and oxygen, influence several physiological processes including aging. One major hallmark of aging is cellular senescence, which is associated with chronic systemic inflammation. Here, we report a chemical tool that generates nitoxyl (HNO) upon activation by ß-galactosidase, an enzyme that is over-expressed in senescent cells. In a radiation-induced senescence model, the HNO donor suppressed reactive oxygen species (ROS) in a hydrogen sulfide (H2S)-dependent manner. Hence, the newly developed tool provides insights into redox cross-talk and establishes the foundation for new interventions that modulate levels of these species to mitigate oxidative stress and inflammation.

A modular scaffold for triggerable and tunable nitroxyl (HNO) generation with a fluorescence reporter.

Nitroxyl (HNO) is a short-lived mediator of cell signalling and can enhance the sulfane sulfur pool, a cellular antioxidant reservoir, by reacting with hydrogen sulfide (H2S). Here, we report esterase-activated HNO-generators that are suitable for tunable HNO release and the design of these donors allows for real-time monitoring of HNO release. These tools will help gain a better understanding of the cross-talk among short-lived gaseous signalling molecules that have emerged as major players in health and disease.