Thiotaurine:From Chemical and Biological Properties to Role in H²S Signaling

In the last decade thiotaurine, 2-aminoethane thiosulfonate, has been investigated as an inflammatory modulating agent as a result of its ability to release hydrogen sulfide (H2S) known to play regulatory roles in inflammation. Thiotaurine can be included in the "taurine family" due to structural similarity to taurine and hypotaurine, and is characterized by the presence of a sulfane sulfur moiety. Thiotaurine can be produced by different pathways, such as the spontaneous transsulfuration between thiocysteine - a persulfide analogue of cysteine - and hypotaurine as well as in vivo from cystine. Moreover, the enzymatic oxidation of cysteamine to hypotaurine and thiotaurine in the presence of inorganic sulfur can occur in animal tissues and last but not least thiotaurine can be generated by the transfer of sulfur from mercaptopyruvate to hypotaurine catalyzed by a sulfurtransferase. Thiotaurine is an effective antioxidant agent as demonstrated by its ability to counteract the damage caused by pro-oxidants in the rat. Recently, we observed the influence of thiotaurine on human neutrophils functional responses. In particular, thiotaurine has been found to prevent human neutrophil spontaneous apoptosis suggesting an alternative or additional role to its antioxidant activity. It is likely that the sulfane sulfur of thiotaurine may modulate neutrophil activation via persulfidation of target proteins. In conclusion, thiotaurine can represent a biologically relevant sulfur donor acting as a biological intermediate in the transport, storage and release of sulfide

Controllable Hydrogen Sulfide Donors and Their Activity against Myocardial Ischemia-Reperfusion Injury

Hydrogen sulfide (H(2)S), known as an important cellular signaling molecule, plays critical roles in many physiological and/or pathological processes. Modulation of H(2)S levels could have tremendous therapeutic value. However, the study on H(2)S has been hindered due to the lack of controllable H(2)S releasing agents which could mimic the slow and moderate H(2)S release in vivo. In this work we report the design, synthesis and biological evaluation of a new class of controllable H(2)S donors. Twenty five donors were prepared and tested. Their structures were based on a perthiol template, which was suggested to involve in H(2)S biosynthesis. H(2)S release mechanism from these donors was studied and proved to be thiol-dependent. We also developed a series of cell-based assays to access their H(2)S related activities. H9c2 cardiac myocytes were used in these experiments. We tested lead donors’ cytotoxicity and confirmed their H(2)S production in cells. Finally we demonstrated that selected donors showed potent protective effects in an in vivo murine model of myocardial ischemia-reperfusion injury, through a H(2)S related mechanism