Inhibition of the DNA-binding activity of NF-
 B by gold compounds in vitro
The authors explain that the “nuclear factor
B (NF-
B) is a transcription factor that is critical for the inducible expression of multiple cellular and viral genes” and “most of the genes known to be activated by NF-
B are involved in the immune and inflammatory responses”. NF-
B-binding to a specific DNA sequence “is essential for the transcription activity of these genes”. The authors had demonstrated previously “that the DNA binding activity of NF-
B is regulated by an oxido-reductive mechanism (redox regulation)”. They “found that oxidation of NF-
B abolished the DNA binding activity and that the subsequent reduction completely restored the activity”.
In this paper the authors “report that gold compounds, especially aurothioglucose (AuTG), have a strong inhibitory effect on NF-
B-DNA binding. Our finding also reveals that Zn2+ is a necessary component of NF-
B for its DNA binding activity and that gold ion can efficiently block NF-
B-DNA binding, presumably through oxidation of the cysteins associated with zinc. This redox mechanism may provide an explanation for the observed efficacy of gold compounds in the treatment of rheumatoid arthritis.”
The authors note “that NF-
B plays a pivotal role in the cytokine network involved in the pathogenesis of RA, and even minimal or partial inhibition of its activity might elicit a substantial effect on inflammatory processes. It is also possible that gold compounds affect multiple transcription factors in addition to NF-
B”.
|
|
