Targeting Calcium Channels to Block Tumor Vascularization
Recent Patents on Anti-Cancer Drug Discovery
The definitive version is available at: La versione definitiva è disponibile alla URL: [inserire URL sito editoriale] Abstract An increasing body of evidence suggests the involvement of hydrogen sulfide (H2S) in different physiological and pathological processes. Similarly to the other gasotransmitters nitric oxide (NO) and carbon monoxide (CO), this bioactive compound is rapidly diffusible through the biological membranes and acts in a paracrine fashion. Despite the large amount of biological
... ount of biological actions observed in vitro and in vivo upon stimulation with H2S donors, as well as by interfering with its synthesis, the molecular targets and mechanisms through which it exerts its intracellular effects are only partially known. A number of proteins are covalently modified by H2S through sulfhydration of specific cysteine residues. However, only in few cases their identity has been discovered and the functional role of this post-translational modification needs to be investigated in more detail. Great attention has been devoted to potassium channels, particularly KATP, as they are considered key mediators of H2S-induced effects, and their sulfhydration has been clearly demonstrated. Recently, different authors reported the ability of H2S to interfere with calcium homeostasis in neurons, cardiomyocytes and endothelial cells. Since calcium signaling is involved in all cell processes, these observations attracted increasing attention from basic biology and medicine. Although some effects of H2S on calcium signals can be ascribed to KATP modulation, there is growing consensus about the existence of other targets for the gasotransmitter. Some of them are Ca 2+ -permeable channels. In this review we discuss the state of the art in this specific field, providing an updated report of H2S interaction with Ca 2+ channels and its functional outcomes.