Fig. 26.
An overview of the cellular signaling processes elicited by H2S donors. The cellular effects of H2S donors can be different, depending on the rate of the H2S release and the targeted versus nontargeted nature of the donor. For example, mitochondrially targeted H2S donors preferentially activate mitochondrial processes (e.g., protection against mitochondrial oxidative stress, or facilitation of mitochondrial DNA repair processes, or electron donation to the mitochondrial electron transport chain) and have lesser effect on cytoplasmatic signaling pathways. High concentrations of mitochondrial H2S donors may also suppress mitochondrial electron transport by inhibiting mitochondrial Complex IV. When fast-acting H2S donors are applied to cells or animals, the initial high H2S concentration may be sufficient to inhibit mitochondrial Complex IV to induce a short-lasting chemical hypoxia, which, in turn, may stimulate compensatory (preconditioning type) processes. Fast-acting H2S donors tend to be more potent activators of cGMP-dependent processes than slow-release H2S donors. Fast-acting H2S donors also tend to exert their action in cooperation with NO synthase-dependent signaling processes. Please note that the downstream pathways activated by the various H2S donors have not yet been characterized in a systematic manner.