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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Mechanism of NF-kappa B translocation in macrophages treated in vitro with cisplatin.

In murine peritoneal macrophages cisplatin (cis-dichlorodiammine platinum (II)), a potent chemoimmunotherapeutic drug modulates the expression of several cytokines which contain nuclear factor kappa B (NF-kappaB) binding site suggesting the involvement of NF-kappaB in the activation process of macrophages by cisplatin. Therefore, we analyzed the effect of cisplatin treatment on NF-kappaB expression and activation in macrophages. The underlying mechanism of NF-kappaB translocation was also investigated. Cisplatin treatment increased cellular NF-kappaB content in macrophages treated for 60 min. NF-kappaB translocation was biphasic. Cisplatin-induced translocation of NF-kappaB took place within 5 min and reached its optimum by 15 min. A second phase of nuclear transfer of NF-kappaB was observed at 3 h of cisplatin treatment which was dependent on H2O2 production in cisplatin-treated macrophages. It was observed that cisplatin-induced NF-kappaB translocation involves serine/threonine phosphatases 1/2A, protein tyrosine phosphatases and genestein sensitive protein tyrosine kinase activities. H-7 sensitive protein kinase C do not fall in the signaling pathway of cisplatin leading to the translocation of NF-kappaB. Both cytosolic and membrane-associated factors were required for the induction of NF-kappaB translocation by cisplatin in macrophages.[1]

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