Ferrous Citrate Up-Regulates the NOS2 through Nuclear Translocation of NFκB Induced by Free Radicals Generation in Mouse Cerebral Endothelial CellsReportar como inadecuado




Ferrous Citrate Up-Regulates the NOS2 through Nuclear Translocation of NFκB Induced by Free Radicals Generation in Mouse Cerebral Endothelial Cells - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Previous studies indicate that the inducible nitric oxide synthase 2 NOS2 of the brain vascular tissue in experimental subarachnoid hemorrhage SAH rats is a critical factor for inducing cerebral vasospasm. However, the underlying molecular mechanisms remain to be elucidated. Here, we applied ferrous citrate FC complexes to the primary cultured mouse cerebral endothelial cell CEC to mimic the SAH conditions and to address the issue how SAH-induced NOS2 up-regulation. Using immunocytochemical staining technique, we demonstrated that NOS2 was expressed in the cultured CEC. Treatment of the CEC with FC induced increases of the intracellular level of ROS, nuclear factor kappa-light-chain-enhancer of activated B cells NFκB nuclear translocation as well as NFκB binding onto the NOS promoter, and the levels of NOS2 mRNA and protein. These effects were abolished by pre-treatment of the cell with N-Acetyl-Cysteine NAC, a reactive oxygen species ROS scavenger. In the present study, two previously predicted NFκB binding sites were confirmed in the NOS2 promoter within the range of −1529 bp to −1516 bp and −1224 bp to −1210 bp. Interestingly, both NFκB binding sites are involved in the FC-activated NOS2 transcriptional activity; the binding site located at −1529 bp to −1516 bp played a greater role than the other binding site located at −1224 bp to −1210 bp in the mouse CEC. These findings highlight the molecular mechanism underlying FC-induced up-regulation of NOS2 in the mouse CEC.



Autor: Li-Ching Chen, Chin Hsu, Chuang Chin Chiueh, Wen-Sen Lee

Fuente: http://plos.srce.hr/



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