Previous results indicated that intravenous injection of copper in the form of a copper–histidine complex in rats triggers the transcriptional induction of the inducible form of nitric oxide synthase (NOS-II). Here, the authors demonstrate that copper activates the transcription factor NF-B in the liver and lung tissues of rats, and that this effect is mediated by oxidative stress, since all copper-induced changes, which include histological alterations, formation of nitrotyrosines, vascular pressure drop, production of tumor necrosis factor- (TNF-), induction of NOS-II and nitrites, are readily prevented by pretreatment of the animals with the antioxidant tempol. By using electrophoretic mobility shift assays, the p50/p65 dimer and higher molecular weight aggregates have been found to be involved in the copper-induced NF-B activation. COX-2, a NF-Bdependent gene involved in the inflammatory response, was also transcriptionally induced by copper, this effect being reduced in the presence of tempol. These results suggest that a physiopathological status, characterized by hypercupremic situations, may lead to the onset of inflammation through production of ROS and activation of NF-B.
Copper activates the NF-kB pathway in vivo
MUSCI, Giovanni
2006-01-01
Abstract
Previous results indicated that intravenous injection of copper in the form of a copper–histidine complex in rats triggers the transcriptional induction of the inducible form of nitric oxide synthase (NOS-II). Here, the authors demonstrate that copper activates the transcription factor NF-B in the liver and lung tissues of rats, and that this effect is mediated by oxidative stress, since all copper-induced changes, which include histological alterations, formation of nitrotyrosines, vascular pressure drop, production of tumor necrosis factor- (TNF-), induction of NOS-II and nitrites, are readily prevented by pretreatment of the animals with the antioxidant tempol. By using electrophoretic mobility shift assays, the p50/p65 dimer and higher molecular weight aggregates have been found to be involved in the copper-induced NF-B activation. COX-2, a NF-Bdependent gene involved in the inflammatory response, was also transcriptionally induced by copper, this effect being reduced in the presence of tempol. These results suggest that a physiopathological status, characterized by hypercupremic situations, may lead to the onset of inflammation through production of ROS and activation of NF-B.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
