Nitric oxide-mediated signaling in pulmonary endothelial cells

摘要: S-nitrosothiol modifications of proteins are emerging as an important nitric oxide-mediated signaling pathway. Our laboratory has focused on S-nitrosation the metal binding protein metallothionein and resulting effects zinc homeostasis, gene expression oxide (NO) mediated in pulmonary endothelium. Statement public health significance: The endothelium is responsible for filtering blood before it enters systemic circulation, such extremely vulnerable to injury by inhaled toxicants environment well those that circulate bloodstream. As constitutively produces NO, we interested studying NO-mediated order lay a foundation will allow us better understand diseases asthma, hypertension sepsis which dysregulation thought be contributing factor disease pathology. To this end have used both recombinant DNA biochemical techniques examine relationship between metallothionein, homeostasis responsive transcription MTF-1. We demonstrated exposure NO results release from turn activates MTF-1, nuclear translocation NO-dependent increases expression. hypothesized sulphydryl groups were cause downstream effects. fluorescent modification biotin switch assay combination with two-dimensional electrophoresis mass spectroscopy extend our study through thiols identify S-nitrosated endothelial cells exposed donor, technique further studies illuminate proteome cells. able several potential targets including cytoskeletal, cytoprotective, glycolytic chaperone proteins. proteomic developed useful screening tool, may lead new insights post-translational proteins, eventually perspectives regarding exacerbated