Biliverdin inhibits activation of NF‐κB: Reversal of inhibition by human biliverdin reductase

摘要: hBVR functions in the cell as a reductase and kinase. In first capacity, it reduces biliverdin, product of HO activity, to effective intracellular antioxidant, bilirubin; dual-specificity kinase (S/T/Y) activates MAPK IGF/IRK receptor signal transduction pathways. NF-κB pathway are activated by ROS, which results activation stress-inducible genes, including ho-1. Presently, we report on negative effect biliverdin converse hBVR. Biliverdin, concentration- time-dependent manner, inhibited transcriptional activity HEK293A cells. Nuclear extracts from biliverdin-treated cells show reduced DNA binding an electromobility shift assay, whereas treated with TNF-α showed enhanced binding. Coimmunoprecipitation data binds 65 kDa subunit NF-κB, that this is dependent TNF-α. Overexpression both basal TNF-α-mediated also NF-κB-activated iNOS gene. Also, overexpression arrested cycle G1/G0 phase number S phase. Similar were observed MCF-7 Because Janus nature inhibitory action present findings provide foundation for therapeutic intervention inflammatory diseases cancer may be attained preventing reduction biliverdin. On other hand, increasing BVR levels beneficial might augmented. © 2007 Wiley-Liss, Inc.