Abstract:
Cell-to-cell communication plays a cardinal role in the biology of multicellular organisms. H2O2 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 H2O2 signals within minutes over long distances, measured in centimeters, in a monolayer of cardiomyocytes. Here we report that this long-distance H2O2 signaling pathway is accompanied by enhanced accumulation of cytosolic H2O2 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 H2O2 signaling pathway that could play an important role in different inflammatory responses, wound responses/healing, cardiovascular disease, and/or other conditions.
摘要:
细胞间通讯在多细胞生物的生物学中起着重要作用。H2O2是一种重要的细胞间信号分子,参与哺乳动物细胞对创伤和其他刺激的反应。我们之前确定了一种信号通路,可以在几分钟内长距离传输伤口诱导的细胞间H2O2信号,以厘米为单位,在单层心肌细胞中。在这里,我们报道了这种长距离的H2O2信号通路伴随着细胞溶质H2O2的积累增强和沿着其路径的细胞中氧化还原状态的改变。我们进一步表明,它需要超氧化物的生产,以及间隙连接的功能,并且伴随着其路径上细胞中数百种蛋白质的丰度变化。我们的发现强调了一个独特而快速的长距离H2O2信号通路的存在,该通路可能在不同的炎症反应中发挥重要作用。伤口反应/愈合,心血管疾病,和/或其他条件。