Discovery Of The Molecular Targets And Mechanistic Study Of The Noxious Effects Of Iodine And Lead Ion

Elemental iodine is an effective broad spectrum antimicrobial that has been used clinically for about two centuries, and it has aslo had an important role in the treatment and prevention of infection. However, a major limitation of its clinical application is that iodine causes noxious stimuli including acute irritation and pain. Recent years, novel preparations of iodine have been developed to control the slow release of a low concentration of free iodine, which helps to minimise the negative side effects. Despite the utility and widespread use of iodine, the molecular mechanism through which iodine mediates its noxious effects remains unknown. By using calcium imaging, our result show that iodine can acitivate TRPA1-mediated extracellular calcium influx in both HEK293 cells and DRG neurons. Further, we expressed hTRPA1 channel gene in xenopus oocyte and HEK293 cells. By using two-electrode voltage clamp and patch clamp, we found that TRPA1-mediated current can be acitivated by iodine. At the animal level, iodine can induce acute pain in pain reaction model, and iodine promote contact dermatitis which SP participates in. In this study, we will investigate the mechanisms of iondine-induced TRPA1 activation and the involvement of TRPA1 in the noxioux effects of iodine. This study not only provides a scientific basis and theoretical foundations for developing new iodine preparations, and also promotes and deepens the the pharmocology research of TRPA1.Pb2+ pollution is a serious health problem. In this study, we find for the first time that Pb2+ inhibits TRPA1 channel in the peripheral nervous system. TRPA1 is a calcium-permeable channel belonging to the TRP family. TRPA1 can be activated by a variety of physical and chemical irritants and plays an important role in diverse physiological and pathological processes. By using calcium imaging, we show that Pb2+ can inhibit TRPA1-mediated calcium influx in both DRG neurons and HEK293 cells. Furthermore, by expressing the human TRPA1 channel gene in Xenopus oocytes and performing two-electrode voltage clamp, we find that Pb2+ can inhibit TRPA1-mediated currents with an IC50 of 2.4μM. This work uncovers a endogenous target of Pb2+ and provides new insight into the molecular mechanisms of Pb2+ neurotoxicity.