Abstract
Background: NO is an important cellular signaling molecule which is derived from L-arginine by nitric oxide synthase (NOS) and the effects of NOS signaling in lung injury is conflicting. The present study was designed to observe the effect of NOS and Arginase signaling in the occurrence and development of lung injury and its mechanism.Methods: An ozone-stressed lung injury animal model was established by exposure to 2.0 ppm O3 for 30 min every day for consecutive 12 day with or without the administration of NO precursor L-arginine or non-selective NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME). Then, the lung histopathology, the releases of inflammatory mediators and the production of ROS were assayed by immunohistochemistry, ELISA and flow cytometry respectively. The activities and expression of NOS and Arginase were assayed by biochemical methods and western blot. Correspondingly, the release of 8-oxoguanine glycosylase 1(8-OxoG) and 8-oxoguanine glycosylase 1 (OGG1) were assayed by ELISA and western blot. The correlation between NOS/Arginase signaling with 8-OxoG/ OGG1 was also analyzed by Pearson correlation coefficients and immunofluorescence in NOS deficient bronchial epithelial cells.Results: In ozone-induced rat lung injury models, lung inflammation as well as lung architecture was disrupted in a time dependent manner. Ozone treatment with L-arginine showed a substantial attenuation of adverse lung histopathological changes and treatment with L-NAME promoted the inflammation and remodeling. Importantly, the expression of NOS was promoted by L-arginine and inhibited by L-NAME and the expression of Arginase was promoted by L-NAME treatment. Further, we observed significantly higher levels of 8-OxoG and lower levels of OGG1 in ozone group which was reversed by L-arginine and promoted by L-NAME. The expression of NOS is closely related with 8-OxoG /OCG1.Conclusion: These findings give further evidence that the NOS signaling is related with base excise repair.
Highlights
Our body communicates with external environment mainly through respiratory tract, gastrointestinal tract, and skin
The expression of nitric oxide synthase (NOS) was promoted by L-arginine and inhibited by L-NAME and the expression of Arginase was promoted by L-NAME treatment
We observed significantly higher levels of 8-OxoG and lower levels of oxoguanine glycosylase 1 (OGG1) in ozone group which was reversed by L-arginine and promoted by L-NAME
Summary
Our body communicates with external environment mainly through respiratory tract, gastrointestinal tract, and skin. Among them lungs are more vulnerable to injury induced by inhaled toxicants on account of its large surface that is constantly exposed to the external environment. Oxidative stress and ROS induced by inflammation can modify proteins, lipids, and DNA. High level of oxidative stress lead to severe damage to DNA and eventually lead to cellular senescence or death. Among these 4 bases of DNA: Cytosine(C), Thymine(T), Adenine(A), and Guanine(G), oxidative damage mostly occurs in guanine base due to its low redox potential. NO is an important cellular signaling molecule which is derived from L-arginine by nitric oxide synthase (NOS) and the effects of NOS signaling in lung injury is conflicting. The present study was designed to observe the effect of NOS and Arginase signaling in the occurrence and development of lung injury and its mechanism
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
