P-274 - Nitrosopersulfide (SSNO­) is a potential protein Cys polysulfidating agent with sustained and long-range effects

Abstract

The biological actions of NO and H2S are intimately intertwined. Chemical interactions of these molecules form a network of cascading chemicals. SSNO­ is a major product of these interactions. It is relatively stable under physiological conditions and not reducible by thiols. Upon slow decomposition of SSNO­, the sulfane sulfur equivalents are released in the form of inorganic polysulfides (HSx­). HSx­ were shown to be important mediators in H2S biology by inducing protein Cys persulfidation. However, HSx­ are readily reduced by the glutathione and thioredoxin systems inside the cell. Importantly, we found that SSNO­ can escape these reducing machineries and hence we hypothesize that it could serve as a sulfane sulfur carrier for sustained and long range HSx­ bioavailability. SSNO­ indeed induced delayed polysulfidation on Cys, GSH, HSA and a slow flux of sulfane sulfur production in HEK 293 cells. Furthermore, HSx­ were shown to activate TRPA1 channels and our experiments revealed that SSNO­ can also function as a TRPA1 activator, but with a lasting effect. These observations give credence to our hypothesis that SSNO­ may be responsible for sustained protein Cys‒polysulfidation and potentially involved in sulfane sulfur trafficking between subcellular compartments.