Propagation of a rapid cell-to-cell HO signal over long distances in a monolayer of cardiomyocyte cells.

Cell-to-cell communication plays a cardinal role in the biology of multicellular organisms. HO is an important cell-to-cell signaling molecule involved in the response of mammalian cells to wounding and other stimuli. We previously identified a signaling pathway that transmits wound-induced cell-to-cell HO signals within minutes over long distances, measured in centimeters, in a monolayer of cardiomyocytes. Here we report that this long-distance HO signaling pathway is accompanied by enhanced accumulation of cytosolic HO and altered redox state in cells along its path. We further show that it requires the production of superoxide, as well as the function of gap junctions, and that it is accompanied by changes in the abundance of hundreds of proteins in cells along its path. Our findings highlight the existence of a unique and rapid long-distance HO signaling pathway that could play an important role in different inflammatory responses, wound responses/healing, cardiovascular disease, and/or other conditions.